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T R E A T M E N T OF HUMAN CANCER W I T H

MUMPS VIRUS
TERUO
ASADA,
MD

Based on confirmation that slightly toxic mumps virus having a strong affinity
with mankind has a carcinostatic effect, it was used in cancer. As priority was
put not on healing but on reconfirmation of its effectiveness against human
cancer and on its mode of administration, patients mostly received only small
amount3 of the virus. Of 90 patients with terminal cancer of various kinds,
treatment was assessed as very good in 37, and good in 42, excluding 11 patients
who had been near death. Administration of mumps virus produced few side-
effects. The initial antineoplastic effect of the mumps virus therapy seemed to
occur rapidly and strongly in proportion to swiftness in proliferation of cancer
cells. Patients retaining physical strength of ten showed continuously suppressed
growth of remaining tumors even after the disappearance of the initial effect,
indicating a possible participation of tumor immunity in the present virus
therapy.
Cancer 34:1907-1928, 1974.

I T HAS BEEN KNOWN FOR QtJlTE SOME TIME


that many viruses have oncolytic effects
on tumor cells, both in experimental animals,
line; streptomycin (lmg/cms), penicillin (1000
U/cm3), and Mycostatin (100 U/cm3) were
added. This salivary solution was stored at
and in some instances, on human t ~ m o r s . ~ 3-lOC.
~ ~ ~ However,
~ this solution was used only
30.31932334 I have previously reported the on- for external or oral administration. In later ex-
colytic effect of mumps virus on Yoshida sar- periments purified mumps virus in tissue cul-
coma in rats.2 These experimental results war- ture medium was received from the Depart-
ranted the testing of mumps virus as a ment of Virology, Research Institute for
therapeutic agent in the treatment of certain Microbial Diseases, Osaka University. Mumps
human cancers, particularly those in which virus was first cultured with monkey kid-
surgery was impossible, and in terminal ney cells (103 TCID,,/O.I ml), but this was
case~.~,3,9 soon given up for fear of mixing of simian
I n this paper I report that mumps virus virus. T h e culture solution of mumps actually
proved to be an effective anticancer agent. I employed was, in most cases, the supernatant
describe in this paper a number of clinical of solution (lo5 TCID,,/O.l ml) obtained by
cases and the therapeutic effects for human its centrifugation after it was cultured for 5 to
cancer of mumps virus. 7 days at 37C in the Eagle medium containing
human albumin (5 mgjcm?), penicillin, and
MATERIALS
AND METHODS streptomycin (or tetracycline) using human
embryonic kidney (HEK) cells. T h e mumps
Mumps virus was collected from the saliva
virus culture solution was stored at 2-5C in
of patients with epidemic parotitis at an early
the liquid form. Infectivity of mumps virus
stage. T h e saliva was purified by filtration, then
was titrated in HEK cells by the hemadsorp-
mixed with an equal amount of glycerin sa-
tion method. T h e titer was read after 7 days
From Osaka University, Osaka, Japan. incubation at 37C.
Address for reprints: Teruo Asada, MD, Department T h e inactivated mumps virus culture solu-
of Virology, Research Institute for Microbial Diseases,
Osaka University, Yamadakami, Suita, Osaka, Japan. tion used for the control solution of this ex-
T h e author expresses his heartfelt thanks t o Prof. periment was inactivated by exposure to
Y. Okuno and Dr. K. Yamanishi, Osaka University:
Prof. Emeritus M. Kurusu and Dr. K. Ueda, Kyoto ultraviolet rays for 5 minutes and then heat-
Prefectuie University of Medicine: Dr. T. Shibata, Dr. ing at 55C for 30 minutes.
Y. Uragami, and Dr. Y. Matsuo, Kyoto First Red Cross Virus solution was administered about 0.5-
Hospital; a n d Prof. M. E. Hodes, Dr. M. W. Taylor,
and Dr. R. K. Togasaki, Indiana University. 30 ml at a dose either topically, intravenously,
Received for publication February 8, 1974. or by inhalation at the time intervals described
1907
1908 CANCERDecember 1974 VOl. 34

in each case. Neutralizing antibody titers of other therapies were avoided in the progress-
the patients’ sera weie determined befoie and observation period, not to mention during this
,ifter administration as far as circumstances therapy, so that an accurate judgment of
permitted. T h e neutralization test was done the ef€ects could be made. Incidentally, a
as previously described by Yamanishi et al.s7 proliferative tendency of tumor cells works
When mumps virus in tissue culture medium as an important factor for MVT, too, and
is used, it is desirable to use concentrated in this sense, the implementation of the above
solutions of fresh cultures akin to a wild rule is necessary. As the mumps virus culture
strain in quality in order to assure anticancer solution contains a minimal amount of peni-
effects. cillin and streptomycin, the patients were
I n practical application of mumps virus to tested for possible hypersensitivity to the
patients, I have used various methods as de- culture solution in advance. All the patients
scribed below, taking full notice of the pa- injected with the mumps culture solution
tients’ general condition, the quality of tumor, received an intracutaneous reaction test in
and its size and location. advance. Currently the virus culture solution
used for intravenous administration is mixed
Application of Virus with tetracycline instead of penicillin and
Extewaal: T h e mumps virus solution is ap- streptomycin for reasons of safety.
plied to the surface of tumor as it is or after
it has been scarified. RESULTS
Local: T h e culture solution of mumps virus
is injected into tumor. (In this and the pre- Nine healthy adults (four men and five
ceding methotls, the greatest care should be women) ranging in age from 35 to 75 were
taken in cleansing the applied region so as given, with their understanding in advance,
not to allow the antiseptic or bactericide to the mumps virus culture solution intrave-
influence the result. nously (three subjects with 5.0 cm3) or sub-
Oial: T h e patient is instructed to take the cutaneously (six subjects with 0.5 cm3). For
mumps virus solution orally as it is, or to take one day following injection, all subjects
bread soaked with the solution. (In case of showed leucocytosis with an especially prom-
esophageal cancer, the lesion is rubbed with inent increase of neutrophilic leucocytes. On
a stringed tampon soaked with the virus solu- the second or third day after injection, most
tion which is then inserted and pulled out. subjects showed leukopenia, with a fall in the
I n case of gastric cancer which is often asso- absolute number of lymphocytes, followed by
ciated with achlorhydria, the patient is in- a gradual return to the normal value.
structed to lie on his left so as to allow the I n both of the above conditions, the re-
xirus solution to remain in the stomach over action seemed stronger in proportion to the
a long time at the time of an empty stomach, increase in the dose injected. When prednis-
with pressure exerted from outside to give the olone, 20 mg, was injected intravenously (three
lesion a better contact with the solution.) subjects) at the time of injection of the cul-
Rectal: T h e mumps virus solution is in- ture solution, there occurred no appreciable
jected into the rectum through the anus. influences on the above reaction. I n addition,
171 travenozrs: T h e culture solution is diiectly there were no remarkable quantitatiye changes
injected into the vein. in led cells, hemoglobin, or serum protein;
Znhalalzon: T h e mumps virus solution is ESR tended to be accelerated in many sub-
sprayed with a nebulizer and inhaled. jects; the subjects felt nothing remarkable
Special attention should be paid to the con- generally or locally. T h e neutralizing antibody
ditions of storage in order to prevent a de- titer in thc blood are indicated in Table 1.
crease of vii ‘11 activity. Needless to say, mumps T h e rise of the antibody titer was speedy
T irus should be handled carefully, to guard in the patient? who previously suffei ed the
against posible spread. As a matter of course, infection with mumps because of booster
special care should be constantly taken in effect.” 3 5 , Z R ?II
the practice of mumps virus therapy ( M V T ) T h e injection of the culture solution into
so that the patients are not influenced by the patients with cancer also produced almost
suggestions. All the anticarcinomatous ther- the same reactions as above, but some patients
apies were as a rule terminated at least 10 showed considerable differences in the degree
days before the practice of this therapy, and and progress.
No. 6 MUMPSVIRUSI N HUMAN
CANCER - Asada 1909
TABLE 1. Neutralizing Antibody Responses in Healthy Adults Injected with Mumps Virus Culture Solution

Qua?tity of
Case Injection virus Neutralizing antibody titer after the injection
no. Age Sex method solution 0 3 6 9 13 18 33days

1 38 F Intravenous 5.0ml 4> 4> 128 128 32 32 32


( + prednisolone)
2 62 F Intravenous 5.0ml 4> 4> 128 128 128 128
3 67 M Intravenous 5.0ml 4> 4> 8 32 32 32
4 36 M Subcutaneous 0 . 5 ml 8 8 16 16 16
5 41 M Subcutaneous 0.5ml 4> 4> 4> 8 32
6 47 F Subcutaneous 0.5ml 4> 4> 4 8 16
7 59 F Subcutaneous 0.5ml 4> 4> 4> 32 128 128
+
( prednisolone)
8 63 M Subcutaneous 0.5ml 4> 4> 4, 8 8 8 8
9 72 F Subcutaneous 0 . 5 ml 4> 4> 4> 4 8 8
+
( prednisolone)

The patients’ neutralizing antibody titers rise within 13 days in cases with local injection
prior to M V T were as weak as 22 or below in and within 7 days in cases with intravenous
most cases. administration. T h e patients took a little
Antibody titers following M V T began to longer than the healthy subjects in the rise

TABLE
2. The Antineoplastic Effect of Mumps Virus
~~ ~ ~

Therapeutic
No. of effects
Type of tumor cases Routes of application ++ + - Adverse reactions
Cutaneous, inclusive 6 Enternal local 5 1
of metastatic C a
Maxillary 4 External 2 1 1
Gingival 1 External 1
Pharyngeal 2 External 2
Laryngeal 1 Inhalation 1
Esophageal 4 Oral 1 3
Gastric 33 Oral intravenous 10 20 3 2 Profuse bleeding (tumor
tissue destruction ?)
Hepatric, iiiclusive 4 Oral intravenous 2 2
of metastatic Ca
Rectal 4 Rectal intravenous 1 3 1 Transient high fever
Pulmonary, inclusive 10 Inhalation intravenous 4 5 1 1 Transient high fever
of metastatic C a
Mammary 2 Intravenous 1 1
Penile 1 External local 1
Uterine 9 External local intravenous 5 2 2 2 Transient high fever
Bone metastases of uterus 1 Local intravenous 1
Ovarian 1 Local intravenous 1 1 Ileus due to peritoneal
adhesion (viral
peritonitis?)
Vaginal 1 Local intravenous 1
Osseous sarcoma 1 External 1
Malignant lymphoma 5 Local 2 2 1
TOTAL 90 37 42 11 7
Classification of therapeutic effects: grade ( ++) means that tumor disappeared or decreased in size to less
than 1/2 of the initial size with subjective symptoms improved; grade (+) means t h a t tumor showed a tendency
of retreat or growth suppression,or t h a t subjective symptoms improved (appetite for food increased, pain improved,
body weight increased, etc.); grade ( - ) means that there were no remarkable effects observed. Many of the
patients falling under ( - ) were near death, and there was not sufficient time left for observations of progress.
1910 CANCERDecember 1974 VOl. 34

FIG. 1. Metastases of
mammary cancer of the
breast skin (Case 1).

of the antibody titer following local injection, mumps virus, but it seemed that this could
probably because the injection was made into be prevented in most cases by preparation
the tumorous tissue. with prednisolone.
Most of the subjects of M V T had terminal Since the virus solution could not be suffi-
cancer. Only if M V T were strongly desired ciently obtained, most of the patients treated
were patients in a comparatively early stage were given only a small quantity of it. I t must
of cancer treated with mumps virus. T h e re- be admitted, therefore, that, in not a few
sults OE application with mumps virus are cases, the trial ended in studies of carcinostatic
summarized in Table 2. effects rather than medicinal treatment. At
A temporary rise of temperature was occa- the beginning of treatment, moreover, the
sionally seen after intravenous injection of virus solution which had been preserved over

Frc. 2. T h e histolog-
ical aspects of the af-
fected parts in Fig. 1
(H & E, ~ 4 0 0 ) .
No. 0 MUMPSVIRUSI N HUMANCANCER * Asada 1911

FIG.3. Case 1 on the


20th day after the start
of RIVT. There is no
tumor on the diseased
skin.

a prolonged period of time was used. There- that the tumor destruction was brought about
fore, it is within the range of possibility that not by mumps virus but by mechanical stim-
a fairly large number of patients has been ulation at the time of application of mumps
given samples of virus with it5 activity already virus (especially in case of terminal cancer).
decreased. Mihere several routes existed in this Therefore, the salivary solution, the mumps
therapy, only one route was tried at the early virus culture solution, the physiological saline
experimental stage in order to see which route solution, and the inactivated culture solution
was effective. I n short, Table 2 does not cor- were applied for inspection directly to the
rectly represent clinical results, but it should area of tumor of the four patients with term-
be taken as a pilot demonstrating how effec- inal cancer. As a result, it was confirmed that
tive the present therapy is. this tumor destructtion was brought about by
I n the meantime, it is possible to imagine mumps virus. T h e above clinical results prove

FIG. 4. T h e histo-
logic aspects of the
treated parts shown in
Fig. 3. Intense reac-
tions are found over
thc canccr cells. Note
the marked tumor cell
necrosis (H & E, ~400).
1912 CANCERDecember 1974 Vol. 34

M V T was manifested more rapidly and accord-


ingly more strongly.
T h e direct use of mumps virus against the
cancer focus is little influenced by the antibody
and its effect is observed at every M V T (see
to Case 4), but the carcinostatic effects can
not be expected i n the intravenous applica-
tion unless a large quantity of virus is ap-
plied in cases where the neutralizing anti-
body is more than 23.
Some illustrative cases are presented below.

CASEREPORTS
Case 1. T h e patient was a 70-year-old
woman with a clinical diagnosis of skin metas-
tases of breast cancer. The histologic diagnosis
was adenocarcinoma.
Three years after an operation for an early
stage of mammary cancer, metastases to the
skin of the anterior thoracic wall were noted.
T h e patient was treated with radiation ther-
apy but did not improve, and was subse-
quently treated with mumps virus from the
12th clay after terminating the radiation ther-
apy. Mumps virus was applied by scarification
over a wide area.
Following daily treatment for 20 clays the
tumor disappeared. The histologic changes are
FIG. 5 . Metastasis of stomach cancer on the abdomi- shown in Figs. 1-4. I n this case, morbid condi-
nal wall (Case 2).
tions were ameliorated earlier at affected re-
gions inoculated with mumps virus earlier.
that mumps virus has anticancer effects irre- This suggests that the anticancerous effcct ob-
spective of the type of human cancer. There served in this case was not clue to the late
was a general tendency that as the prolifera- response of radiotherapy b u t due to the action
tion of tumor was more vital, the effect of of mumps virus. However, she also had a large

FIG. 6. T h e histo-
logic aspects of the tu-
mor shown in Fig. 5
(H & E, ~ 4 0 0 ) .
NO. 6 hlurws VIRUSIN HUMAN
CANCER - Asuda 1913
number of metastatic foci in the lungs accom-
panied by carcinomatous pleuritis, antl died
;il,out (imonths after tlic treatment a t a metl-
i a l ceiiter.
Case 2. This patient was a GG-year-old man.
T h e clinical diagnosis was skin metastases of
stornach cancer, and the histologic diagnosis,
adenocarcinom a .
T h e patient, operated on for stomach cancer
1 year previously, had metastases along thc
entire abdominal wall (Figs. 5 ant1 6). After
injection of 0.5 ml aliquots of cultured virus
into five areas of the tumor on two successivc
days, tlestruction of tumor tissue was observed.
Tissue destruction appeared several days after
initiation of treatment, and became more re-
markable daily. By the 7th day the tumor ap-
peared as indicated in Figs. 7 and 8. (No
tlestruction was observed at the site of the
injection of the control solution.) Althougli
the patient died of general metastases on the
18th clay of treatment, it appears that tlestruc-
tion of tumorous tissue was caused by mumps
virus inoculation.
Case 3. T h e patient was a 58-year-old
woman. Her clinical diagnosis was gingival
cancer, with a histologic diagnosis of epider-
moid carcinoma.
Phyma (1.5 x 1.5 x 1.7 cm) which orig-
FIG. 7. Tumor (Case 2) on the i t h day after M V T .
inated from the erosion at the right lower Destruction of tunior tisrue is found.
wisdom tooth was diagnosed as cancer of the
transitional epithelium in a medical center.
T h e patient refused to be sent to the hospital procedure similar to vaccination for 20 con-
antl strongly desired to be treated with M V T secutive days.
as an outpatient. Mumps virus culture solu- As shown in Figs. 9-12, disappearance of
tion was applied to the affected parts by a the carcinomatous cells of the tumor was ap-

I:ic. 8. T h e histologic
aspccts o f the treated
canccr tissue shown in
Fig. 7. Hypochromatic
nucleus and signct ring
cell (partially degen-
erated) are observed.
(H 8r E, x400).
1914 CANCERDecember 1974 VOl. 34

of the tongue, did not improve, owing to the


difficulty of applying virus caused by inter-
ference by the tongue and saliva. (Intravenous
administration of the culture solution was not
yet in practice at that time.)
Subsequently, the patient was treated with
conventional therapies. She died of general
metastases 1 year and 5 months after MVT.
Case 4. This patient was an 82-year-old
woman. Her clinical diagnosis was cutaneous
cancer, with a histologic diagnosis of basal cell
carcinoma.
A birthmark o n the face had suddenly en-
larged. I t is shown in Figs. 14 and 15. Cuta-
neous cancer was diagnosed at a medical cen-
ter, but her family did not consent to an
operation because of the patient’s advanced
age. T h e lesion was treated by local applica-
tion of 1 cm3 of mumps virus salivary solution,
followed by local injection of 0.5 cm3 of the
culture solution in divided doses. T h e local
application of the virus was repeated five
times at intervals of 2 to 3 days. T h e tumor
began to decrease in size on approximately
the 4th day of treatment, and its central part
was destroyed in about 50 days as shown in
Figs. 16 and 17.
Treatment was then interrupted, although
the tumor was only partially cured, and she
FIG. 9. Gingival tumor in the area of the right lower received no additional treatment. Two and a
wisdom tooth (Case 3). half years later she visited us again. Her gen-
eral condition was excellent with no detect-
parent on the 13th day of the treatment. T h e able metastases. T h e remaining tumor was
tumor nearly completely disappeared on the no longer hyperplastic, but appeared only
23rd day (Fig. 13). Erosion, which ranged from slightly bigger than it had been at the time
the internal side of the gingiva to the back side treatment was interrupted (Fig. 18). T h e tu-

FIG. 10. The histo-


logic aspects of the tu-
mor tissue shown in
Fig. 9 (epidermoid car-
cinoma) (H & E, x400).
No. G MUMPSVmus IN HUMAN
CANCER - Asada 1915
inor was treated with the same course of M V T
as before. Despite an increased antibody titer
against mumps viru5 (neutr,ilihg antibody
25), the tumor responded favorably to tieat-
ment (Fig. 19). It is now more than 3% years
since the first consultation, and she is still leatl-
ing a normal life.
Case 5. T h e patient was an 84-yeai-old
woman, with a clinical diagnosis of cutaneous
cancer, and a histological diagnosis of sclua-
mom cell cai cinoma.
A birthmark on the patient's left uppei
arm had enlarged during the last 20 years.
I n the middle of February, 1969, granulo-
matous tissue suddenly appeared from a part
of the birthmark, and it rapidly swelled up
ant1 extended, as indicated in Figs. 20 and 21.
It was diagnosed as cutaneous cancer in a
medical center. T h e patient visited a hospital
desiring to be treated with M V T as an out-
patient.
T h e tumor was treated by local application
of 1 ~1113of mumps virus salivary solution once
a day, together with local injection of the cul-
ture solution (2 cm3 divided into small por-
tions and injected into several spots), followed
by local application alone for 5 days. T h e tu-
mor was reduced to one-third its original size
in about 1 month (Figs. 22 and 23). I n this
case as in Case 4, the tumor lost its hyper-
plastic nature, and the lesion remained alniost FK. 1 1 . Note the marked regression of the tumor
unchanged and no metastases were recognized. (Case 3) with MVT (after 13 days).
Her general condition remained good for the
subsequent 2 years without further treatment.
ical diagnosis of malignant lymphoma, with a
,It the end of this period she died of cerebral
histologic diagnosis of reticulosarcoma.
hemorrhage from hypertension.
Lymph nodes on the lateral sides of the pa-
Case 6. This 43-year-old female had a clin- tient's neck began to swell one after another

FIG. 12. The histo-


logic aspects of tumor
tissue shown in Fig. 11:
epitheliomatous hyper-
plasia of the gingiva.
No malignant features
are piesent (H Rc E,
~400).
1916 CANCERDecember 1974 Vol. 34

FIG. 13. Tumor (Case 3) is extremely difficult to lo-


cate (23rd day after the start of MVT). FIG. 14. Malignant tumor in the face (Case 4).

with no other symptoms. I n about 1 month, tion and chemotherapy in a medical center
the nodes ranged in size from 1.5 x 1.0 x 1.0 with little effect. Because of side effects, other
cm to 3.0 x 2.5 x 2.5 cm. At this time, the therapy was terminated and mumps virus was
above diagnosis was made. She received radia- tried from the 12th day after the termination.

FIG. 15. T h e histo-


logic aspects of the tu-
mor shown in Fig. 14
(H & E, x400).
No. 6 MUMPSV I R U S IN HUMANCANCER * Asada 1917
One of the lymph nodes was chosen, and 0.5
cm3 of the mumps virus culture solution was
divided into five portions and injected into
five separate parts of the node once a day for
the following 3 days. As seen from Figs. 24-26,
the treated node regressed almost completely
in 10 days. I n this connection, the fact that
the anticancerous effect was observed only in
the lymphoma subjected to M V T demon-
strates evidently that the effect noted in this
case was not due to a late response to radio-
therapy or chemotherapy but to the action
of mumps virus.
There were no remarkable side effects. T h e
patient was later treated in various ways in
a medical center, with little result, and
died after about 6 months due to systemic
metastases.
Case 7. This patient, a 54-year-old man,
had a clinical diagnosis of malignant lym-
phoma, and histologic diagnosis of reticulo-
sarcoma.
While under hospitalization for multiple
enlarged lymph nodes of the neck and armpit,
the patient developed leukopenia. His general
condition deteriorated following chemother-
apy (vinblastine sulfate) and radiation. After
a pause of 13 days, the previous regimen was
replaced by MVT. Because of a shortage of
the mumps virus culture solution, only one
large lymph node (12 cm across) in the right FIG. 16. T u m o r (Case 4) treated with MVT. (after
armpit was chosen (Figs. 27 and 28). This was 50days).
treated by local application of 0.1 cm3 of the
culture solution to each of five different areas reaction for several days after treatment. Local
of the node. T h e same procedure was repeated reduction of the node became gradually ap-
on the next day. There was n o remarkable parent; it soon regressed as shown in Fig. 29.

FIG. 17. T h e histo-


logic aspects of the
treated canccr tissue
shown in Fig. 16. Hy-
pochromatic nucleus
and swelling of cyto-
plasm are observed (H
& E, x400).
1918 CANCERDecember 1974 VOl. 34

(Fig. 31). T h e patient remained healthy and


without stomach symptoms for about 10
months following treatment, when he sud-
denly developed a cerebral embolism. He did
not recover consciousness after hospitaliza-
tion and died after several days.

Case 9. This patient was a 46-year-old


woman. Her clinical diagnosis was uterine
cancer (recurrent), and her histologic diag-
nosis, squamous cell carcinoma.
T h e patient had an operation for advanced
cervical cancer. T h e operation was supple-
mented by radiation therapy. About 3 months
after the operation, however, the patient began
to complain of pain in the affected region,
together with bleeding, while the carcinoma-
tous tumor reached as far as the vaginal wall
and caused a prominent swelling, especially at
the right side of the vagina (Figs. 32 and 33).
These lesions responded only poorly to anti-
carcinomatous agents and radiation therapy.
Anemia and leukopenia became more promi-
nent.
On the 11th day after the termination of
an anticarcinomatous therapy, the patient re-
ceived 30 cmRof the mumps virus culture soIu-

FIG. 18. The figure of the remaining tumor (Case 4)


at 2.5 years after M V T (slightly bigger than i n Fig. 16,
but with no metastases).

During therapy of the single node all of the


untreated nodes continued to enlarge, so that
treatment was switched from MVT to radia-
tion and chemotherapy. T h e patient died in
about 1 year.

Case 8. T h e patient was a 61-year-old man,


with a clinical diagnosis of stomach cancer.
T h e patient was referred to a medical cen-
ter for examination because of an unpleasint
feeling in the stomach and deterioration in his
nutritional condition. Examination demon-
strated a large tumor extending to the g e a t e r
curvature (Fig. 30). We recommended an
operation, but failed to get consent from his
family. We were thus compelled to carry out
M V T . T h e patient received about 2 cm" of
the mumps virus salivary solution for oral use
five times a t intervals of 3 days. Subjective
symptoms began to improve from the 3rd day
of treatment, and nausea disappeared soon
after, followed by an increased appetite for
food and gradual improvement of nutritional
status (body weight was increased by 1.8 kg in
a month). Roentgenographic examinations on
the 45th day revealed a significantly reduced Frc.. 19. T h e figure of the tumor (Case 4) ictreatctl
tumor a t the aoove-mentioned medical center with MVT (after 10 days).
No. 6 MUMPSVIRUSIN HUMANCANCER * Asada 1919

FIG.20. Cutaneous cancer on left upper arm (Case 5). FIG.22. T u m o r (Case 5 ) on the 30th day after M V T .
Note the marked regression of the tumor.

tion intravenously 30 minutes after the hyper- allergic reactions to the vaccine, and to facili-
sensitivity test, and prednisolone, 20 mg 1.v. tate virus infection.) No other anticarcinoma-
(This was used in order to suppress possible tous therapy was given after the single intra-

FIG. 21. T h e histo-


logic aspects of the tu-
mor tissue shown in
Fig. 20 (H k E, ~ 4 0 0 ) .
1920 CANCERDecember 1974 Vol. 34

FIG. 23. T h e histo-


logic aspects of the tu-
mor (Case 5 ) treated
with MVT (H & E,
x400).

venous injection. Pain and bleeding regressed extent shown in Figs. 34 and 35 after 2 weeks.
almost completely, and the swelling in the T h e patient’s general condition improved pro-
vagina began to subside 1 week after the in- gressively, and the partially remaining tumor
jection. Her condition was improved to the was confirmed to have no proliferative tend-
ency with periodic gynecologic examinations,
while it was showing a favorable progress. (In
passing, the anticancerous effect mentioned
above is presumed not to be attributable to
a late response to radiotherapy or chemother-
apy whatsoever, in consideration of the fact
that the growth of tumor could not be inhib-
ited and systemic conditions were aggravated
despite the long-term radiotherapy or chemo-
therapy and that the morbid conditions showed
further exacerbation after discontinuation of
the above therapy.) About 6 months after
MVT, the patient suddenly developed renal
insufficiency and died of uremia about a month
later.

FIG. 24. Malignant lymphoma on the left side of FIG. 25. T h e histologic aspects of the lymphoma
the neck (Case 6). (Casc 6) (H & E, ~ 4 0 0 ) .
No. 6 MUMPSVIRUSIN HUMANCANCER Asnda - 1921

FIG. 26. Lymphoma (Case 6) on the 10th day after FIG. 27. Malignant lymphoma of the right armpit
MVT. (Case 7).

Case 10. This 58-year-old woman had a c h i - T h e patient visited our clinic for a tumor
cal diagnosis of mammary cancer, with a his- within the left mamma. She looked well in
tologic diagnosis of adenocarcinoma. her nutritional conditions with nothing re-

FIG. 28. T h e histo-


logic aspects of the tis-
sue in diseased IvmDh
node (Case 7) (H’&’E,
x400).
1922 CANCERDecember 1974 VOl. 34

markable systemically. Locally, the nipple was


prominently depressed, with swelling of 6.0 x
5.0 x 3.0 cm, oval shaped and firm with an
uneven surface. I n addition, several lymph
nodes swollen to the size of 1.5 x 1.0 x 1.0 cm
were palpable at the armpit. Results of exami-
nations (roentgenography, ultrasonography,
and histologic examination) are shown in Figs.
36-38. I recommended an operation, to which
her family did not consent, but strongly asked
me to carry out her MVT, which I did. On
the 1st day, the patient routinely received the
hypersensitivity test and intravenous adminis-
tration of prednisolone, followed by intra-
venous administration of the mumps virus cul-
ture solution (20 cm3), which was given for the
following two consecutive days (3 doses in all).
From the 3rd day after the start of intravenous
administration, the patient had continuous
pain and burning sensation at the focus, both
of which retreated in about 2 days. When 1
week passed, the tumor began to show regres-
sion with partial softening. As this tendency
became more apparent afterwards, the patient’s
pain gradually disappeared, while the swollen
lymph nodes at the armpit became smaller
and were no more palpable after 2 weeks. Ex-
aminations conducted on the 20th day of treat-
ment showed remarkable results (Figs. 39 and
40). (The tumor was reduced to less than one-
FIG. 29. Reduced tumor (Case 7) on the 10th day
after MVT.

FIG. 31. Roentgenographic examination of the Stom-


ach (Case 8) on the 45th day after MVT. Reduction
FIG. 30. Roentgenograph of stomach cancer (Case 8). of filling defect was confirmed.
No. 6 MUMPSVIRUSIN HUMANCANCER - Asada 1923

FIG. 32. Tumor on


the right side of the
vagina (Case 9).

third of initial volume.) Moreover, the pres- at the time of the operation for some unknown
ent therapy did not produce any ill effects in reasons. Figure 41 shows the histologic pattern
her general conditions. at the time of the operation. T h e patient of
Then the patient and her family consented this case is, of course, still alive.
to the radical operation for mammary cancer
because they thought that her conditions were
satisfactory enough to withstand the opera- DISCUSSION
tion. Postoperatively, she showed a very favor-
able progress. It was reported by the surgeon Although many reports have been published
in charge that the naturally expected swelling suggesting the treatment of human cancers by
of the lymph nodes concerned was not observed use of viruses with a selective oncolytic effect,

FIG. 33. The histo-


logic aspects of the tu-
mor tissue shown in
Fig. 32 (H & E, ~400).
1924 CANCERDecember 1974 Vol. 34

FIG.34. Affected part


(Case 9) on the 14th
day a f t e r M V T .
Marked regression of
tumor is observed.

practical application of viral cancer therapy of the virus against the tumorous cells
has not been reported to date. T h e reasons were carried out under conditions quite
for this may be considered as follows: different from those of the human body,
and the crucial question of whether the
1. T h e life of a patient may be endang- virus has a strong sensitivity to the human
ered by the virus used. body20 has not been studied.
2. Oncolytic effects may not be lasting
because antibodies against the virus are Since orchitis accompanies epidemic paro-
produced during the course of treat- titis6 only after pubertyloJ9 or during the
menteZ3 period of active multiplication of germ cells,
and the parenchyma of the testicle is so com-
3. Most of the experiments on the action pletely damaged by orchitis that sterility per-

FIG. 35. T h e treated


cancer tissue (Case 9)
with MVT. Note the
marked atypism of tu-
mor cells with pyknotic
nucleus, karyolysis,
swelling of cytoplasm,
and vacuolar degenera-
tion (H & E, X4GO).
No. 6 MUMPSVmus IN HUMANCANCER= Asada 1925

FIG.37. Ultrasonic graph. T h e tumor area is between


the arrows (Case 10).

cancer cells.’ I t is needless to say that the


strong affinity of mumps virus with flourish-
ingly proliferating cells does not always lead
to infection and destruction of such cells.
Differences in the affinity of mumps virus
with individual organs, relations with hor-
mones, immunologic factors, amount of virus,
and various other factors are naturally ex-
pected to influence the mechanism. (Hema-
FIG. 36. Roentgenograph of mammary cancer (Case togenous tissues and the embryo of a preg-
10). nant woman affected by m u m p ~ may ~ ! ~be~
taken as good examples.)
sists throughout life,35 I assumed that mumps As is generally known, epidemic parotitis
virus would have an affinity and a destructive is not a fatal disease and causes no sequelae
power to vigorously multiplying cells such as in the infected organs (salivary glands, pan-

FIG. 38. T h e histo-


logic aspects of the tu-
mor tissue shown in
Fig. 36. Note high cel-
lularity (H gi E, x400).
1926 CANCERDecember 1974 Vol. 34

is a minimum amount, there is very little pos-


sibility of causing a serious ~ondition.l~,~"28,36
I therefore considered it reasonable to use
mumps virus for the treatment of advanced
cancer.
Subjective symptoms of many patients im-
prove (especially regression of pain and an
increased appetite for food) temporarily just
a few days after the initiation of MVT for
some unknown reasons. Mie, however, cannot
jump to the conclusion that these symptoms
are characteristic of this therapy. T h e subse-
quent anticarcinomatous effect characteristic
of ,MVT may be divided into two actions from
an analysis of the clinical results. One is the
cell destroying action which begins to take
place several days after administration of
mumps virus, and the other is the tumor sup-
pressing action which continues long after-
wards.
Some investigators try to explain the first
phenomenon (cell destroying action) only
from the view of interferon. I cannot agree
to this view, because, on the one hand, symp-
toms of cancer are rarely improved by the
virus infections where interferon is generally
thought to be produced, and because the local,
destructive, strong carcinostatic action can be
FIG. 39. T h e tumor shadow of roentgcnograph observed even if mumps virus is administered
(Case 10) on the 20th day after the start of M V T . diiectly to the site of tumor, which is known
Note LIIC change of form and area on the tumor to have poor productivity of interferon.5.18 On
shadow.
the other hand, there is no evidence yet found
that the first phenomenon has something to
creas, meninges etc.) except the testicle.10 As
do with the endocrine system.
most people in the age subject to cancer have
antibodies for mumps virus,lO." even iE that Since the anticancer effect of mumps virus
is also found in the patient who has no
antibody for mumps, and since the inacti-
vated mumps virus vaccine does not show
the notable tumor destruction that the live
vaccine does, it is therefore difficult to ex-
plain the first phenomenon of the M V T
with respect to the effect caused by the allergic
reaction (delayed hyper~ensitivity).~3
In the long run, it would be justifiable to
conclude that the essence of the above-men-
tioned cell destroying action might be attrib-
utable, as demonstrated by the results so far
obtained,Z.s to the oncolytic effect of mumps
virus.
Generally speaking, malignant tumor, if
treatment is interrupted, shows reproliferation
after a while in most cases. I n case of MVT,
as mentioned above, the cell destroying action
FIG. 40. T h e ultrasonic graph of the treated mam-
mary cancer (Case 10). T h e tumor size is markctlly comes t o an end in a short time because of
reduced (arrows). the resistance mainly coming from immunity.
No. 6 MUMPSVIRUSIN HUMANCANCER - Asnda 1927

FIG. 41. T h e histo-


logic aspects in the
tumor tissue treated
with M V T (Case 10).
hlarked pleoinorphism
of cytoplasm and n u -
cleus (partially de-
stroyed) in scattered
tumor cells is observed
(H & E, X400).

But there is little tendency of reproliferation ments have a great importance, for these re-
over a long time subsequently even if the re- sults indicate the possibility that tumor anti-
maining tumor is left untreated. Systemically, gen may also be produced in the human body
many patients (19 cases) have remained un- to suppress the growth of tumor in response
symptomatic for a long time (some patients to a strong antigen originating from tumor
leading a normal life for more than 3 years), cells infected with virus, only if there are dis-
which is indeed remarkable. turbances neither in the nonspecific mecha-
I t is from this point that I have made the nisms of host defense nor in the immunologic
conclusion that M V T has not only the above- mechanism.
mentioned initial effects but also a continu- O n the basis of this view, I think it justi-
ously tumor-suppresing effect. Since the ap- fiable to conclude that the above-men tioned
pearance of this effect was limited to the continuous carcinostatic effect in M V T is at-
patients with good general conditions, I pre- tributable to this tumor immunity.
sumed that the reticuloendothelial system It may be said as a conclusion that MVT
(RES) might participate in this effect. should be tried in patients having early can-
T h e presumption is based on the reports14, cer who have been under n o influence of any
2 4 ~ ~that
7 stimulation and activation of RES other anticancer therapy with their RES not
may prevent animal tumors from occurring so severely damaged, using large doses of virus
or occasionally produce therapeutic effects, a t an early stage when the obstacle against
and that tumor immunity can be established in virus is not so immense yet, with attention
anirnals~~13~1iJ1 which have been immunized being paid to stimulation of RES.
with a strong antigen (tumor-specific trans- If we improve h l V T with reference to the
+
plantation antigens virus antigen) obtained results of the fundamental and clinical ex-
from tumorous cells infected with virus. periments which have been made today, while
As human cancer is, in general, of spon- we make an effort to discover the carcinostatic
taneous occurrence and a long time has elapsed viruses similar to mumps virus and to apply
before formation of tumor, it is said that there them one after another, the carcinostatic ef-
has already occurred a disturbance in the im- fect of the virus therapy will be increased.
munologic mechanism of the Iiost.1~12~1fl So it Further, if a different carcionostatic therapy
is difficult to expect that experimental results (preferably one not clamaging RES) is addi-
obtained in artificial animal cancer may also tionally practiced, a more hopeful way may
take place in human cancer. Nevertheless, the be opened to the therapeutic approach for
above-mentioned results of animal experi- cancer to meet the needs of patients.
1928 CANCERDecember 1974 VOl. 34
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