Advancing Cell Therapies for Solid Tumors: A Pathway to Overcome Biological, Operational, and Regulatory Hurdles.

Abstract

Cellular therapies have revolutionized the treatment of hematologic malignancies and are now emerging as potentially promising interventions for solid tumors. While considerable learnings can be leveraged from hematologic applications to inform the development of cell therapies in solid tumors, a number of biological and operational challenges-such as target-antigen heterogeneity; off-tumor target-mediated toxicity; immunosuppressive microenvironment; limited trafficking and persistence; tissue accessibility; and significantly larger patient populations-necessitate innovative clinical, manufacturing, regulatory, and operational strategies to deliver effective cell therapies for solid tumors. This white paper, informed by the 2025 Summit on Advancing Cell Therapy for Solid Tumors-co-sponsored by American Society for Transplantation and Cellular Therapy (ASTCT) and Society for Immunotherapy of Cancer (SITC)-proposes a framework for cellular therapy development in solid tumors, with an emphasis on logistical, operational, and regulatory considerations unique to this setting. The paper lays out an innovative, collaborative operational model to leverage collective experience and knowledge; emphasize standardization; invest in both prospective and retrospective banking of materials; engage in regulatory data-driven recalibration; engage payers before therapy begins; and establish regional manufacturing hubs and tailored accreditation pathways to support scalability and quality assurance. Operational innovations that can streamline access include hub-and-spoke clinical networks-where a central specialized facility is connected to smaller, more accessible locations-as well as early patient referrals. To safely implement new therapies, it is essential for providers to undergo enhanced training to manage cellular therapy-specific and delayed toxicities. Regulatory recalibrations-including streamlined evaluation of long-term follow-up requirements and proactive payer engagement for comprehensive reimbursement-are equally vital. Finally, cell therapy experts must lead cross-disciplinary education to ensure equitable and safe access as indications for cellular therapy expand across solid-tumor types, autoimmune diseases, and other disease types. Collaborative efforts across clinical, operational, regulatory, and policy initiatives are vital in order to unlock the full potential of cellular therapy for diverse patient populations.