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Meet the Author: Roisin E. O'Cearbhaill, MD — ‘Advancing Cell Therapies for Solid Tumors: A Pathway to Overcome Biological, Operational, and Regulatory Hurdles’

Roisin E. O'Cearbhaill, MD, is the last author of “Advancing Cell Therapies for Solid Tumors: A Pathway to Overcome Biological, Operational, and Regulatory Hurdles.” She shares in this Q&A background on how this research came about, lessons learned, and how these findings are guiding current and future initiatives.

Read on for this perspective, and then visit Transplantation and Cellular Therapy, the official journal of ASTCT, for the full article.

Nucleus: What inspired the development of this white paper, and what gaps in the field of solid tumor cell therapy were you aiming to address?

Roisin E. O'Cearbhaill, MD, (RO): This white paper grew out of a shared sense that cellular therapy for solid tumors is entering an exciting new phase. We have witnessed remarkable successes with these therapies in hematologic malignancies, and we're now seeing tremendous momentum across a wide range of solid tumors. At the same time, it became clear that many of the biological, operational, and regulatory approaches developed for blood cancers cannot simply be applied to solid tumors. We wanted to bring together experts from across the field to identify the challenges ahead, share lessons learned, and help create a practical roadmap for moving the field forward.

The ASTCT-SITC collaboration provided a unique opportunity to bring together leaders from academia, industry, regulatory agencies, manufacturing, and patient care to develop a roadmap for the field. Our goal was not simply to identify challenges, but to outline practical solutions and establish best practices that can accelerate safe, equitable, and scalable implementation of cellular therapies for patients with solid tumors.

Nucleus: How can lessons learned from hematologic malignancies be effectively translated to advance cell therapies for solid tumors?

RO: The success of CAR T-cell therapy in hematologic malignancies provides an invaluable foundation. We learnt how to build cell therapy programs, manage complex toxicities, establish quality standards, and create multidisciplinary care pathways.

Rather than simply mirroring the approaches used in hematologic malignancies, we need to thoughtfully adapt those lessons to the unique realities of solid tumors. The principles of standardized care, rigorous toxicity management, accreditation, and coordinated networks remain highly relevant, but they must be tailored to address issues such as tumor heterogeneity, tissue procurement, and the unique biology of the solid tumor microenvironment.

Nucleus: What are the most significant biological barriers—such as tumor heterogeneity or the immunosuppressive microenvironment—that must be overcome in solid tumor applications?

RO: The biggest biological hurdles include tumor antigen heterogeneity, limited trafficking and persistence of therapeutic cells, as well as the extremely immunosuppressive tumor microenvironment. Solid tumors tend to be much more complex and variable than hematologic malignancies, making it difficult to identify targets that are both effective and safe. In addition, physical barriers within tumors can limit immune cell infiltration, while suppressive immune and stromal components can impair cellular therapy function once cells arrive at the tumor site. Overcoming these barriers will require next-generation engineering approaches, improved target selection, combinatorial strategies, and a deeper understanding of tumor biology.

Nucleus: Your paper emphasizes cross-specialty collaboration—what practical steps are needed to foster effective partnerships between hematologists, oncologists, and other stakeholders?

RO: The successful integration of cellular therapy into solid tumors will require a truly multidisciplinary approach, much like the evolution of immunotherapy over the past decade. Rather than being confined to a single specialty, progress will depend on close collaboration among cellular therapy specialists, medical oncologists, hematologists, surgeons, pathologists, immunologists, radiologists, pharmacists, advanced practice providers, and nurses, each bringing essential expertise.

Practically, this means creating multidisciplinary working groups, developing shared educational programs, establishing common treatment pathways, and encouraging cross-training. As cellular therapies expand into solid tumors and potentially autoimmune diseases, experienced cellular therapy teams play a critical role in transferring knowledge and best practices across specialties.

Nucleus: Why is standardization of cell collection, assays, and biospecimen banking so critical, and how can the field move toward achieving this?

RO: Standardization is essential for both scientific progress and patient care. There is considerable variability in tissue collection, leukapheresis procedures, manufacturing processes, and biomarker assessments across institutions. That variability makes it difficult to compare outcomes, optimize processes, and meet regulatory requirements.

Similarly, early and systematic biospecimen banking creates opportunities to better understand mechanisms of response and resistance while ensuring high-quality starting material for future manufacturing. Standardized approaches can improve reproducibility, support regulatory harmonization, and ultimately accelerate innovation.

Nucleus: The concept of hub-and-spoke clinical networks is highlighted—how could this model improve patient access to cell therapies?

RO: One of the greatest barriers to equitable access is geography. Many patients live far from specialized cellular therapy centers and may not be able to travel repeatedly for treatment. 

Hub-and-spoke models offer a practical solution. Specialized centers can serve as hubs for manufacturing, training, regulatory aspects and complex care, while community sites function as spokes that support referrals, monitoring, and aspects of treatment closer to home. This approach allows us to expand access while maintaining safety, quality, and expertise.

Nucleus: What infrastructure and manufacturing innovations, such as regional hubs, are most important for scaling solid tumor cell therapies?

RO: We need both manufacturing innovation and operational innovation. Priorities include automated and closed-system manufacturing platforms, shorter production timelines, streamlined quality testing, improved chain-of-custody systems, and development of regional manufacturing hubs.

Long term, the field is also exploring allogeneic and off-the-shelf approaches that could dramatically improve scalability. Collectively, these advances aim to reduce costs, shorten turnaround times, and bring therapies to larger patient populations more efficiently.

Nucleus: How should physician training evolve to ensure safe management of both acute and delayed cell therapy toxicities?

RO: Education must evolve alongside the therapies. Many solid tumor oncologists have limited experience with cellular therapy-specific toxicities such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), hemophagocytic lymphohistiocytosis (HLH), delayed cytopenias, and emerging product-specific adverse events. 

Training should include structured curricula, simulation-based learning, case-based education, and standardized toxicity-management algorithms. Importantly, education should extend beyond physicians to nurses, physician assistants, pharmacists, patients, and caregivers to ensure rapid recognition and management of complications.

Nucleus: What regulatory and reimbursement challenges currently limit access, and how can early engagement with regulators and payers help address these barriers?

RO: Both regulation and reimbursement remain major challenges. While these safeguards are important, the current requirements around long-term follow-up, accreditation, companion diagnostics, and manufacturing can place substantial demands on treatment centers. At the same time, reimbursement is often inconsistent, leaving institutions and patients navigating coverage gaps and delays that can ultimately affect access to care.

Early engagement with regulators can help develop more risk-adapted frameworks that maintain safety while reducing unnecessary complexity. Likewise, proactive collaboration with payers can support sustainable reimbursement models that reflect the realities of cellular therapy delivery and expand patient access

Nucleus: Looking ahead, what are the most critical steps needed to ensure equitable, safe, and scalable access to cellular therapies across diverse patient populations?

RO: The future will depend on all of us working together. Scientific advances alone won't be enough. We need the right infrastructure, education, regulatory pathways, reimbursement models, and clinical networks to ensure patients can actually access these therapies. The collaboration between ASTCT and SITC that led to this white paper is a great example of the type of partnership the field needs. By bringing together expertise from academia, industry, regulators, and patient advocates, we can help ensure that cellular therapies reach their full potential for patients with solid tumors.

Roisin E. O'Cearbhaill, MD

Roisin E. O'Cearbhaill, MD, is an associate attending gynecologic medical oncologist and section head of Solid Tumor Cell Therapy at Memorial Sloan Kettering Cancer Center, with a joint appointment at Weill Cornell Medical College. Her research focuses on the development of innovative immunotherapy and cellular therapy approaches for gynecologic cancers, including ovarian, cervical, and endometrial cancers. She leads and collaborates on early-phase clinical trials, cooperative group studies, and national and international research initiatives aimed at advancing novel therapeutics and expanding patient access to cutting-edge cancer care. Dr. O'Cearbhaill served as senior author of the ASTCT-SITC white paper, Advancing Cell Therapies for Solid Tumors: A Pathway to Overcome Biological, Operational, and Regulatory Hurdles, which provides a roadmap for the safe, scalable, and equitable implementation of cellular therapies in solid tumors.