CANCER

Chapter 6: Immunotherapy
 CANCER: AN INTRODUCTION

▰ In the 1950s, Dr.

▰ Stimulation of the William Coley showed
immune systems has he could control the
long been important in growth of some
the treatment of cancers with an
cancer. To survive and injection of a mixed
grow, cancerous cells vaccine to strep and
must overcome the staph bacteria. His
surveillance of the concoction is known as
immune system. Coley’s toxin.
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 CANCER: BCG

▰ A nonpathogenic
mycobacterium, known
as Bacillus Calmette-
Guerin (BCG),
stimulates cell-
mediated immunity. It
is used as a vaccine
against tuberculosis,
as well as a treatment
for bladder cancer.
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 CANCER: INTERFERONS

▰ Cytokines important to immune function are

also used nonspecifically. Recall that interferon
is secreted by virus-infected cells to impede the
invasion of adjacent cells. You can now
produce interferon in large amounts by using
bioengineering techniques. One form of
interferon (interferon-alpha) is commonly used
for some myeloma, myelogenous leukemia,
hairy cell leukemia, and malignant melanoma.
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 CANCER: INTERLEUKINS

▰ Recall that interleukins are chemicals

secreted by one leukocyte (white blood
cell) to stimulate other leukocytes. One
type, interleukin-2, is used to treat kidney
cancer and melanoma. Unfortunately,
these therapies, especially the
interleukins, have side effects, usually,
flu-like symptoms.
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 CANCER: TUMOR ANTIGENS

▰ Inducing the victim’s immune system to attack

tumors is difficult because tumor antigens are
tolerated by the immune system because these
antigens are self-antigens. One strategy is to
induce the patient’s own dendritic cells to
represent the tumor antigens as foreign.
Circulating dendritic cells are removed from the
patient’s blood and mixed with kidney cancer
cells in a laboratory.
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 CANCER: TUMOR ANTIGENS
▰ The cells are then ▰ Dendritic cell vaccines
injected back into the
patient as a vaccine.
These cells have been
therefore primed to
present the antigen to
antibody-producing cells
and augment an immune
response.
have been shown to
be effective in
treatment of some
kidney cancers. This
treatment regiment
has also shown
promise in melanoma
trials. 7
 CANCER: THE MAGIC BULLET

▰ The advances in monoclonal antibody therapy have fueled the search for the
mythical “magic bullet” – these are cytotoxic weapons that will seek and kill
only the cancer cells. The magic bullet continues to evade us. This may be
because we are using only one weapon in an arsenal of weapons, or it may be
because tumors are diverse, hardy, and hard to kill.

▰ Also, tumors tend to be unique. With

many tumors, each cancer victim
would need his or her own unique
antibody.
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 CANCER: IMMUNOTHERAPIES

▰ However, laboratory studies have

shown that vaccination with lymphoma-
associated proteins can stimulate the
immune systems of mice to resist the
development of lymphomas. There
have been some clinical successes in
people using the protein vaccines,
especially with leukemias and
lymphomas.
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 CANCER: IMMUNOTHERAPIES

▰ Other immunotherapies include the use of a monoclonal

antibody against cell-surface antigens. Examples include
rituximab (Rituxan), used in a treatment of non-Hodgkin’s
lymphoma and directed against the CD20 antigen found
on the surface of both normal and malignant B-
lymphocytes. A monoclonal antibody against a receptor
found predominately on breast tumors, trastuzumab
(Herceptin), is useful against certain breasts cancers. 10
 CANCER: IMMUNOTHERAPIES EXAMPLES

Herceptin is
Rituximab is
used to treat
used to treat
breast
NHL (Non-
cancers.
Hodgkin’s
Lymphoma). 11
 CANCER: HER-2

▰ Again, the use of mABs has experienced some

complications due to the relatively nonspecific
nature of their actions. Herceptin is active
against the HER-2 receptor that is
overexpressed on some but not all breast
cancers (Figure 6-7). HER-2 is a growth
receptor and its presence may be linked to the
abnormal growth patterns of the cancer
tissue. 12
 CANCER: HER-2

▰ However, HER-2 receptors

▰ Clinical trials are ongoing
are also present on some
to study the effectiveness
normal tissues. A relatively
of linking toxins and
high frequency of
antibodies that are directed
cardiovascular
at cancer cell antigen,
complications has been
killing cells in the vicinity.
reported in the patients
receiving Herceptin. The
mABs may be attacking the
HER-2 receptors on normal
heart cells. 13
Figure 6-7. ACTION OF HERCEPTIN AGAINST
BREAST TUMORS AND OTHER CELLS

Breast Breast Destruction

tumor cell tumor cell of tumor
cell

HER-2 receptor
mABs
against Compromise
HER-2 of heart cell
Heart cell Heart cell and possible
cardiovascular
problems
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