Immunotherapy of sarcomas with modified T cells.
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Embargo End Date
ICR Authors
Authors
Mahalingam, P
Julve, M
Huang, P
Furness, AJS
Pollack, SM
Jones, RL
Julve, M
Huang, P
Furness, AJS
Pollack, SM
Jones, RL
Document Type
Journal Article
Date
2022-07-01
Date Accepted
2022-07-01
Abstract
PURPOSE OF REVIEW: To summarize the development of modified T-cell therapies in sarcomas and discuss relevant published and ongoing clinical trials to date. RECENT FINDINGS: Numerous clinical trials are underway evaluating tumor-specific chimeric antigen receptor T cells and high affinity T-cell receptor (TCR)-transduced T cells in sarcomas. Notably, translocation-dependent synovial sarcoma and myxoid/round cell liposarcoma are the subject of several phase II trials evaluating TCRs targeting cancer testis antigens New York esophageal squamous cell carcinoma-1 (NY-ESO-1) and melanoma antigen-A4 (MAGE A4), and response rates of up to 60% have been observed for NY-ESO-1 directed, modified T cells in synovial sarcoma. Challenges posed by modified T-cell therapy include limitations conferred by HLA-restriction, non-immunogenic tumor microenvironments (TME), aggressive lymphodepletion and immune-mediated toxicities restricting coinfusion of cytokines. SUMMARY: Cellular therapy to augment the adaptive immune response through delivery of modified T cells is an area of novel therapeutic development in sarcomas where a reliably expressed, ubiquitous target antigen can be identified. Therapeutic tools to improve the specificity, signaling, proliferation and persistence of modified TCRs and augment clinical responses through safe manipulation of the sarcoma TME will be necessary to harness the full potential of this approach.
Citation
Current Opinion in Oncology, 2022, 34 (4), pp. 362 - 370
Source Title
Current Opinion in Oncology
Publisher
LIPPINCOTT WILLIAMS & WILKINS
ISSN
1040-8746
eISSN
1531-703X
1531-703X
1531-703X
Collections
Research Team
Mol and Systems Oncology
Skin Unit
Skin Unit