Cellular therapies in sarcoma and other solid tumors
- PMID: 40423031
- DOI: 10.1097/CCO.0000000000001152
Cellular therapies in sarcoma and other solid tumors
Abstract
Purpose of review: While adoptive cell therapies such as chimeric antigen receptor T (CAR-T) cell have demonstrated efficacy in hematological malignancies, their success in solid tumors remains challenging due to tumor heterogeneity, antigen specificity, and the suppressive tumor microenvironment. This review aims to provide an overview of recent advancements in cellular therapies, in sarcomas and other solid malignancies.
Recent findings: In the field of sarcomas, the approval of afamitresgene autoleucel (afami-cel) for synovial sarcoma in Atoxiciugust 2024 marks a milestone in T cell therapy, demonstrating an objective response rate (ORR) of 39% and a median overall survival (OS) of 16.9 months in the SPEARHEAD-1 phase 2 trial. Other trials exploring NY-ESO-1 specific T-cell receptor-engineered T (TCR-T) therapies in myxoid round-cell liposarcoma (MRCL) have shown promising response rates. Beyond sarcomas, CAR-T therapies targeting CLDN18.2 in gastrointestinal cancers, GD2 in gliomas, and PSCA in prostate cancer have demonstrated varying degrees of efficacy, with ongoing research to date.
Summary: Clinically, these therapies highlight the need for improved patient selection criteria, and optimized antigen targeting. Toxicity management must also be taken into account, as cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) can be severe. Further studies should focus on improving safety and T cell persistence, and refining manufacturing processes to increase accessibility and scalability.
Keywords: CAR-T cell; Cellular therapies; Sarcoma; Solid tumors; TCR-T cell.
Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.
Similar articles
-
Review of Adoptive Cellular Therapies for the Treatment of Sarcoma.Cancers (Basel). 2025 Apr 12;17(8):1302. doi: 10.3390/cancers17081302. Cancers (Basel). 2025. PMID: 40282478 Free PMC article. Review.
-
Afamitresgene autoleucel for advanced synovial sarcoma and myxoid round cell liposarcoma (SPEARHEAD-1): an international, open-label, phase 2 trial.Lancet. 2024 Apr 13;403(10435):1460-1471. doi: 10.1016/S0140-6736(24)00319-2. Epub 2024 Mar 27. Lancet. 2024. PMID: 38554725 Free PMC article. Clinical Trial.
-
Advances in CAR T cell therapy: antigen selection, modifications, and current trials for solid tumors.Front Immunol. 2025 Jan 6;15:1489827. doi: 10.3389/fimmu.2024.1489827. eCollection 2024. Front Immunol. 2025. PMID: 39835140 Free PMC article. Review.
-
Enhancement of anti-sarcoma immunity by NK cells engineered with mRNA for expression of a EphA2-targeted CAR.Clin Transl Med. 2025 Jan;15(1):e70140. doi: 10.1002/ctm2.70140. Clin Transl Med. 2025. PMID: 39763064 Free PMC article.
-
Expanding the Therapeutic Reach of Chimeric Antigen Receptor T-Cells and Bispecific T-Cell Engagers Across Solid Tumors.JCO Precis Oncol. 2025 Mar;9:e2400753. doi: 10.1200/PO-24-00753. Epub 2025 Mar 26. JCO Precis Oncol. 2025. PMID: 40138603 Review.
References
-
- Savina M, Le Cesne A, Blay JY, et al. Patterns of care and outcomes of patients with METAstatic soft tissue SARComa in a real-life setting: the METASARC observational study. BMC Med 2017; 15:78.
-
- Pollack SM, Somaiah N, Araujo DM, et al. Clinical outcomes of patients with advanced synovial sarcoma or myxoid/round cell liposarcoma treated at major cancer centers in the United States. Cancer Med 2020; 9:4593–4602.
-
- Hong DS, Van Tine BA, Biswas S, et al. Autologous T cell therapy for MAGE-A4+ solid cancers in HLA-A∗02+ patients: a phase 1 trial. Nat Med 2023; 29:104–114.
-
- D’Angelo SP, Araujo DM, Razak ARA, et al. Afamitresgene autoleucel for advanced synovial sarcoma and myxoid round cell liposarcoma (SPEARHEAD-1): an international, open-label, phase 2 trial. Lancet 2024; 403:1460–1471.
-
- Sidaway P. Afami-cel provides a novel treatment option for rare sarcoma subtypes. Nat Rev Clin Oncol 2024; 21:401.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials