N E W S & A N A LY S I S

From the Analyst’s Couch

The clinical pipeline for cancer cell

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therapies

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Samik Upadhaya, Jia Xin Yu, Monica Shah, Diego Correa,
Tanya Partridge and Jay Campbell
Earlier this year, idecabtagene vicleucel The T cell receptor (TCR) T cell therapy 23% and 56%, respectively) compared with
(Abecma), a chimeric antigen receptor class added 80 new agents, followed by the significant increases observed in the pre-
(CAR)-​T cell therapy targeting B cell natural killer (NK)/NKT cells (67) and vious year (51%, 83% and 80%, respectively).
maturation antigen (BCMA) was approved novel T cells (51). Most (835) cell therapies Reasons behind such a sharp year-​on-​year
by the FDA for the treatment of multiple are of autologous origin, with twice as decline in the number of agents across these
myeloma, becoming the first CAR-​T cell many autologous agents in development as targets could include market satu­ration and the
therapy for a target other than CD19 to allogeneic agents (Supplementary Fig. 1). impact of COVID-19 on drug R&D. The top
receive approval. There are currently five cell There was a significant increase in the solid tumour targets explored remain largely
therapies approved by the FDA, all of which number of allogeneic agents in preclinical and the same, with undisclosed tumour-associated
are CAR-​T cell therapies. This analysis gives early-​clinical (phase I) development in the antigen (TAA) being at the top. Most of the
an updated view of the cancer cell therapy past year (48% and 42%, respectively), more agents for solid tumours use CAR-​T cell
landscape, including the global R&D pipeline modest than the increase observed the year modalities enhanced to overcome the chal-
of agents, the status of clinical trials, and before (80% and 95%, respectively). There lenges associated with recognition, trafficking
real-​world data evidencing their current use was, however, a higher increase in allogeneic and surviving in the tumour microenviron-
in clinical practice. cell therapy agents in phase II development ment. Of note, development of cell therapy
(48%) compared with last year (33%). For agents targeting glypicans 2 and 3 (GPC2 and
Steady growth of the R&D pipeline most cell therapy agents in phase II and GPC3) continues its fast growth, nearly dou-
As of 16 April 2021, there were 2,073 active beyond in regions outside the United States, bling each year since 2019 (Supplementary
cell therapy agents in the global pipeline, such as China, it has not been disclosed Fig. 3). Most of this acti­vity is in liver cancer, as
572 more than the previous update in 2020. whether they are autologous or allogeneic glypicans are highly expressed in hepatocellular
This represents a 38% increase in the past (Supplementary Fig. 2). carcinomas.
year compared with a 48% increase from
2019 to 2020. Among the different types Top targets for cell therapy agents. We explored Cell therapy trial landscape
of cell therapy, CAR-​T cells continue to targets and pathways for cell therapy agents. According to data pulled from
dominate the landscape with 299 new agents CD19, BCMA and CD22 remain dominant ClinicalTrials.gov, as of April 2021 there
added to the pipeline, a 35% increase from targets for haematological indications (Fig. 2), are 1,358 active cell therapy trials; this
2020 (Fig. 1). Most CAR-​T cell agents (80%) but the rise in the number of agents pursuing represents an increase of 43% from 2020
are at the preclinical and phase I stage. these targets in the past year is modest (15%, to 2021, compared with a 24% increase from
2019 to 2020 (Supplementary Fig. 4). Most
Therapy type Year
2021 652 276 226 1,164 of that growth has been due to CAR-​T cell
CAR-T cell 2020 462 215 182 865 clinical trials (which have increased 83%
2019 264 150 147 568 since our 2019 update) along with more trials
2021 122 181 testing ‘other cell therapies’, TCR T cells, and
NK/NKT cell 2020 73 114
2019 49 77 tumour-​infiltrating lymphocytes. The number
2021 102 149 of trials testing NK/NKT cells dropped
Novel T cell
technology
2020 64 98 off and has not fully recovered. Similar to
2019 53 previous years, most trials are focusing on
TAA/TSA- 2021 90
2020 79 haematological malignancies, and 40% of
targeted
T cell 2019 61 trials are for solid tumours (Supplementary
2021 151 214 Fig. 5), most of which are in early stages.
TCR T cell 2020 85 134 This is probably a reflection of the inherent
2019 58 98
2021 40 73 Development stage challenges of using cell therapies for solid
TIL cell 2020 44 Marketed tumours. Some examples from early-​phase
2019 34 Phase III clinical readouts of recent data outputs are
134 35 202 Phase II
Other cell
2021
Phase I promising (Supplementary Table 1).
2020 114 167
therapies
2019 84
Preclinical We also researched which sites are
120
handling most of the trials. We found that all
0 100 200 300 400 500 600 700 800 900 1,000 1,100 1,200 the top hospitals and universities conducting
Number of active therapies cell therapy trials are located in the United
Fig. 1 | Changes in the cancer cell therapy pipeline. Comparison of cell therapy agent development States (Fig. 3), indicating that, despite a global
pipeline across various therapy types from 2019 to 2021. NK, natural killer; TAA, tumour-associated interest in cell therapies, the United States
antigen; TCR, T cell receptor; TIL, tumour-​infiltrating lymphocyte; TSA, tumour-​specific antigen. remains the leader in trial administration.

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a Top targets in haematological malignancies b Top targets in solid tumours

2021 222 237 2021 14 5 11 26 4 3 3 66
CD19 2020 194 206 TAA 2020 15 5 11 27 4 3 65
2019 126 136 2019 17 11 21 3 6 62
2021 81 2021 30
BCMA 2020 58 66 2020 3 20 25
HER2
2019 34 36 2019 3 14 19
2021 39 42 2021 4 21 26
CD22 2020 26 27 MSLN 2020 19 21
2019 15 15 2019 13 16
2021 32 2021 22
CD20 2020 23 26 GD2 2020 17 21
2019 16 19 2019 14 18
2021 23 23 2021 20 23
CD123 2020 21 22 EGFR 2020 16 18
2019 16 16 2019 14 17
2021 16 2021 25
TAA 2020 17 GPC2/3 2020 14 17
2019 17 2019 6 7
2021 15 18 2021 12 17
CD33 2020 13 16 NY-ESO-1 2020 9 14
2019 14 2019 11 13
2021 16 2021 15
CD30 2020 14 MUC1 2020 12 13 Therapy type
2019 99 2019 8 10 CAR-T cell
2021 17 2021 13 14 NK and NKT cell
CD38 2020 9 11 PSMA 2020 10 11 Novel T cell technology
2019 9 10 2019 TAA/TSA-targeted T cell
5 6 Other cell therapies
2021 10 2021 9 TCR T cell
CS1 2020 8 EBV 2020 4 8 TIL cell
2019 66 2019 3 4 8
0 50 100 150 200 250 0 20 40 60
Number of active therapies Number of active therapies
Fig. 2 | Top targets of cell therapies for blood and solid tumours. Targets in haematological malignancies (part a) and targets in solid tumours
(part b). NK, natural killer; TAA, tumour-​associated antigen; TCR, T cell receptor; TIL, tumour-​infiltrating lymphocyte; TSA, tumour-​specific antigen.

Global development pipeline academic institutions and industry in the years. Whereas cell therapy clinical trials are
The United States and China continue to United States and China remains largely accruing, real-​world data show that there
dominate the cell therapy development the same to the previous year: most agents was a decrease in the number of patients
pipeline with a total of 791 and 695 agents (83%) in the United States are being developed in clinical practice receiving cell therapies,
in each region, respectively (Supplementary in industry, whereas in China the split is more especially during the height of the pandemic
Fig. 6). The cumulative number of cell even (60% industry and 40% academic). in 2020. With stabilization of COVID-19
therapies in development increased by 31% cases and the evolution of the clinical, social
in the United States and 40% in China versus CAR-​T cell real-​world data and economic landscape, we are seeing
an increase of 40% and 69%, respectively, We used a IQVIA proprietary database an upturn in the number of cell therapy
from 2019 to 2020, consistent with an overall containing US medical and prescription claims trials being launched. Given continued
reduced spike in the number of agents (from to assess the number of patients receiving improvements in managing COVID-19 and
48% to 38% as previously mentioned). The CAR-​T cells in clinical practice based on CPT ongoing innovation in the field of oncology
distribution of cell therapy assets among and ICD-10 codes (Supplementary Fig. 7). cell therapy, the promise of cell therapy
We noted a marked decline in the number remains.
MD Anderson 172 of patients receiving CAR-​T cells during
the months of March and April 2020, which Samik Upadhaya1 ✉, Jia Xin Yu1, Monica Shah2,
MSKCC 86 Diego Correa2, Tanya Partridge2 and Jay Campbell1
Mayo Clinic
coincided with the first wave of the COVID-19
78 1
Anna-​Maria Kellen Clinical Accelerator, Cancer
National Institutes pandemic in the United States. This may have
77 Research Institute, New York, NY, USA.
of Health reflected instability in the health-​care system 2
IQVIA, Durham, NC, USA.
City of Hope 76 during the initial wave of COVID-19, a
University of ✉e-​mail: supadhaya@cancerresearch.org
Minnesota 69 decline in the use of more elective therapies,
https://doi.org/10.1038/d41573-021-00100-​z
Dana Farber
Cancer Institute 65 a decrease in availability of staff and resources
University of to support CAR-​T cell-​related procedures, Competing interests
Pennsylvania 64
Sarah Cannon
and an unwillingness of both patients and M.S., D.C. and T.P. are full-​time employees at IQVIA. The
Research Institute 59 medical staff to expose patients with refractory other authors declare no competing interests.

Texas Children’s 59 disease to a potentially high-​risk hospital Supplementary information

Hospital The online version contains supplementary material available
0 40 80 120 160 environment. at https://doi.org/10.1038/d41573-021-00100-​z.
Number of clinical trials

Fig. 3 | Top 10 cell therapy development Conclusions Related links

sites. The United States remains the leader in Our current analyses indicate that the clinical Cancer Research Institute Dashboard for Cancer Cellular
trial administration. MSKCC, Memorial Sloan development of cellular therapies continues, immunotherapy: https://www.cancerresearch.org/scientists/
immuno-​oncology-​landscape/cancer-​cell-​therapy-​landscape
Kettering Cancer Centre. albeit at a slower pace compared to previous

504 | JULY 2021 | volume 20 www.nature.com/nrd

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