Cancer Biology & Therapy

Engineering T Cells: From Mechanism to Medicine

Chimeric antigen receptor (CAR)-T cell therapy has redefined cancer immunotherapy. By re-engineering a patient's own T cells to recognize tumor antigens, CAR-T has delivered deep, durable, and curative responses in B-cell malignancies, including relapsed or refractory leukemias, lymphomas, and multiple myeloma, where conventional therapies had failed. This success has motivated efforts to improve the safety and efficacy of CAR-T in more cancers, to extend engineered cell therapy into non-malignant diseases such as autoimmunity, and to remove inefficiencies in how these therapies are made. Increasing evidence indicates that durable therapeutic efficacy depends not only on receptor design but also on the molecular programs governing T-cell activation, metabolism, persistence, differentiation, and long-term fitness. This Collection brings together advances across the CAR-T landscape, from next-generation constructs and combination strategies to entirely new manufacturing paradigms. Together, these developments hope to move this technology from a narrow set of hematologic indications toward a broad, accessible platform for reprogramming the immune system against disease.

Despite its transformative clinical success, CAR-T therapy remains constrained by an incomplete understanding of the biological mechanisms that govern durable T-cell function. While receptor engineering has advanced rapidly, long-term therapeutic efficacy depends on coordinated regulation of signaling pathways, immunological synapse formation, metabolism, mitochondrial fitness, epigenetic remodeling, and cell-state transitions that collectively determine persistence, exhaustion, and functional longevity. These mechanisms are particularly critical in solid tumors, where chronic antigen stimulation and immunosuppressive microenvironments impair T-cell activity, but they are equally important for emerging applications including autoimmune diseases, regenerative medicine, and in vivo T-cell engineering. At the same time, scalable manufacturing has emerged as a scientific challenge in its own right, with growing recognition that activation and expansion conditions profoundly influence therapeutic quality. A deeper mechanistic understanding of T-cell biology, coupled with advances in biomaterials, synthetic biology, computational modeling, and manufacturing technologies, will be essential for developing the next generation of safe, durable, and broadly accessible engineered T-cell therapies.

This Collection welcomes original research, reviews, and perspectives that advance the mechanistic understanding, engineering, and clinical translation of CAR-T and related engineered T-cell therapies. We particularly encourage studies that elucidate the biological mechanisms governing T-cell fate and function, including receptor signaling, immunological synapse organization, metabolism, mitochondrial fitness, persistence, exhaustion, differentiation, epigenetic regulation, and cell-state programming. We also welcome advances in enabling technologies such as synthetic receptor design, genome engineering, biomaterials, cytokine engineering, manufacturing science, artificial intelligence, computational modeling, and in vivo T-cell engineering that improve the predictability, scalability, and therapeutic performance of engineered cells. Finally, we invite translational studies spanning hematologic malignancies, solid tumors, autoimmune diseases, and other emerging applications that establish broadly applicable principles for next-generation engineered immune therapies.

Dr. Adam Snook is a Professor in the Departments of Pharmacology, Physiology, & Cancer Biology and Microbiology & Immunology at Thomas Jefferson University and Co-Leader of the Immune Cell Regulation and Targeting Program of the Sidney Kimmel Comprehensive Cancer Center. He is a cancer immunologist developing new immunotherapies for cancer and other human diseases. His work has led to investigator-initiated clinical trials examining colorectal cancer chemoprevention, cancer vaccines, and CAR-T cell therapies.

Dr. Xiao Huang is an Assistant Professor at Drexel University, where he leads the Precision Immune Engineering Laboratory. His research combines biomaterials, synthetic immunology, and nanotechnology to engineer extracellular signals that program immune cell fate and function. His laboratory pioneered programmable DNA-scaffolded biomaterials for CAR-T cell extracellular programming, demonstrating that precise nanoscale organization of receptor ligands can sustain CAR-T expansion, preserve memory-associated states, and retain anti-tumor function. More broadly, his group develops precision biomaterials to uncover fundamental design principles governing immune modulation and biologic delivery across adaptive and innate immune systems.

­­All manuscripts submitted to this Article Collection will undergo a full peer-review; the Guest Advisor for this Collection will not be handling the manuscripts (unless they are an Editorial Board member).

Please review the journal scope and author submission instructions prior to submitting a manuscript.

The deadline for submitting manuscripts is 31st May 2027.

Please contact Rebecca Turner at rebecca.turner@tandf.co.uk with any questions or requests for discount codes relating to this Article Collection.

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