Future Directions and Priorities for Cellular Therapy in Sarcoma: A Report from the Strategic Advances in Sarcoma Science Cell Therapy Breakout

Jacqueline Oliva-Ramirez¹, David Milewski², Lauren Banks³, Kelly M Bailey⁴, Everett J Moding⁵, Jessica Lake⁶, Alice Chen⁷, Jessica D Daley⁴, Erin E Resch^{6

8}, Rosandra N Kaplan⁶, Brian H Ladle⁸, Lindy Zhang⁸, Margaret M Chou⁹, Rosa Nguyen⁶, Urania Dagalakis⁶, Nourhane Al Akoum¹⁰, Poul H Sorensen¹¹, Jonathan A Fletcher¹², Ronald DeMatteo¹³, Nicolas J Llosa⁸, Seth M Pollack¹⁰

Affiliations

¹ Department of Translational Molecular Pathology, MD Anderson Cancer Center, Houston, TX 77030, USA.
² Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
³ Sarcoma Medical Oncology Service, Memorial Sloan Kettering Cancer, New York, NY 10065, USA.
⁴ Division of Pediatric Hematology-Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15215, USA.
⁵ Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA.
⁶ Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
⁷ Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
⁸ Division of Pediatric Oncology, Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
⁹ Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia and the Perelman School of Medicine, Philadelphia, PA 19104, USA.
¹⁰ Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
¹¹ Department of Pathology and Laboratory, University of British Columbia, Vancouver, BC V5Z 1L3, Canada.
¹² Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
¹³ Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

PMID: 41008910
PMCID: PMC12469009
DOI: 10.3390/cancers17183068

Review

Future Directions and Priorities for Cellular Therapy in Sarcoma: A Report from the Strategic Advances in Sarcoma Science Cell Therapy Breakout

Jacqueline Oliva-Ramirez et al. Cancers (Basel). 2025.

. 2025 Sep 19;17(18):3068.

doi: 10.3390/cancers17183068.

Authors

Affiliations

¹ Department of Translational Molecular Pathology, MD Anderson Cancer Center, Houston, TX 77030, USA.
² Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
³ Sarcoma Medical Oncology Service, Memorial Sloan Kettering Cancer, New York, NY 10065, USA.
⁴ Division of Pediatric Hematology-Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15215, USA.
⁵ Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA.
⁶ Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
⁷ Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
⁸ Division of Pediatric Oncology, Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
⁹ Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia and the Perelman School of Medicine, Philadelphia, PA 19104, USA.
¹⁰ Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
¹¹ Department of Pathology and Laboratory, University of British Columbia, Vancouver, BC V5Z 1L3, Canada.
¹² Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
¹³ Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

PMID: 41008910
PMCID: PMC12469009
DOI: 10.3390/cancers17183068

Abstract

Background: In September of 2024, the 2nd annual meeting of the Strategic Advances in Sarcoma Science (SASS) convened at the National Institutes of Health. This gathering of national sarcoma experts focused on preclinical studies, clinical trials, opportunities, challenges, and future directions in sarcoma biology and clinical care with a focus on immunotherapy. The Immunology in Sarcoma breakout group conducted a dedicated discussion focused on the current and future implementation of adoptive cellular therapies (ACTs) in sarcomas. The current manuscript summarizes these discussions and provides a comprehensive resource for researchers and clinicians.

Results: Adoptive cell therapy (ACT) has shown encouraging results in sarcomas with afami-cel achieving durable responses in synovial sarcoma and early TCR-T trials against NY-ESO-1 and MAGE-A4 demonstrating meaningful response rates. Building on these outcomes will require discovering new targets, selecting optimal cell types, refining conditioning regimens, combining with alternative treatment strategies such as TKIs, and leveraging predictive biomarkers informed by a deeper understanding of the tumor microenvironment.

Conclusions: Sarcomas are promising targets for adoptive cell therapy (ACT), as shown by afami-cel's success in synovial sarcoma, but broader impact requires new target discovery, optimal cell selection, improved conditioning, combination treatments, deeper tumor microenvironment understanding, and predictive biomarkers to achieve more durable responses for more patients.

Keywords: TCR; adoptive cellular therapies (ACTs); chimeric antigen receptor; immunotherapy; sarcoma.

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Conflict of interest statement

Over the past two years, Seth Pollack has consulted for or participated in advisory boards with Attivare, EMD Serono, Bayer, Rain Therapeutics, Deciphera, Boehringer Ingelheim, Springworks, Adaptimmune, Ipsen, Daiichi-Samkyo, and Replimmune. He has given paid speakers bureau presentations for Deciphera and Springworks. His lab has a sponsored research agreement with Obsidian Therapeutics. Kelly Bailey serves a Data and Safety Monitoring Committee (DSMC) member for Merck. Margaret Chou serves on the scientific advisory board of Merlin Biotech.

Figures

**Figure 1**
Adoptive cell therapy in sarcoma: modalities, targets, trials and challenges. Created in BioRender by Oliva-Ramírez, J. (2025) www.biorender.com (accessed on 1 September 2025).

**Figure 2**
Cell product production begins with blood draw, often in the form of a apheresis (left); a certain cell type may be purified, engineered and expanded before ultimately being re-infused back to the patient. Created in BioRender by Oliva-Ramírez, J. (2025) www.biorender.com (accessed on 1 September 2025).

See this image and copyright information in PMC

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Future Directions and Priorities for Cellular Therapy in Sarcoma: A Report from the Strategic Advances in Sarcoma Science Cell Therapy Breakout

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Future Directions and Priorities for Cellular Therapy in Sarcoma: A Report from the Strategic Advances in Sarcoma Science Cell Therapy Breakout

Authors

Affiliations

Abstract

Conflict of interest statement

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