Beyond CARs: New T-Cell Strategies Take Center Stage

Richard C. Koya, MD, PhD
Published: Thursday, Jan 18, 2018
VCURichard C. Koya, MD, PhD
Richard C. Koya, MD, PhD
 
Associate Professor, Oncology
Associate Director, Center for Immunotherapy
Director, Vector Development & Production Facility,
Roswell Park Comprehensive Cancer Center,
Buffalo, NY
Strategic Partnership
Recent advances in the understanding of the immune system are paving the way for new and effective approaches to treating cancer. This is highlighted by FDA approvals in 2017 of T lymphocyte–based adoptive cellular transfer (ACT) therapies that use chimeric antigen receptors (CARs) to target CD19, a protein that is expressed on the surface of tumor cells.

The T cells fueling these exciting therapies are created by transduction, in which a viral vector is used to induce the expression of a transgene. In the case of the 2 newly approved therapies, tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (Yescarta), the transduction payload consists of single-chain variable fragments derived from an antibody that reacts against CD19. The transformed T cells develop added signaling domains that ensure activation of T cells once they find their target cancer cells. Because CD19 is expressed on the surface of B-cell leukemia/lymphoma cells and has limited expression in normal cells (mainly B lymphocytes), it was considered an ideal target.

The Focus Shifts to New Targets

The race to develop CAR T cells now focuses on discovering additional targets. Finding proteins on the surface of tumor cells that are not present in normal tissues has been extremely challenging—especially in the case of solid tumors—decreasing the prospects for a safe CAR therapy for solid tumors. However, another modality of engineered T cells has been in development, although it has received much less attention than CAR T cells: T-cell receptor T cell-based ACT (TCR-T ACT).
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View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Archived Version of a Live Webcast: Virtual Current Trends™: European Perspectives on the Advancing Role of CAR T-Cell Therapy in Hematologic MalignanciesJun 29, 20192.0
Community Practice Connections™: Practical Application of Sequencing for EGFR-Mutant Lung Cancers: A Focus on Recent Evidence and Key Next Steps in TrialsJun 29, 20192.5
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