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T-Cell Engineering for Cancer Immunotherapy

Sadelain, Michel MD, PhD

doi: 10.1097/PPO.0b013e3181c51f37
Practice of Oncology: Recent Advances

The adoptive transfer of tumor-reactive cells is a promising approach for the treatment of melanoma and some other cancers. To remedy the difficulties associated with the isolation and expansion of tumor-reactive T cells in most cancer patients, peripheral blood T cells can be retargeted to any chosen tumor antigen by the genetic transfer of an antigen-specific receptor. The transduced receptors may be human leukocyte antigen-restricted, heterodimeric T-cell antigen receptor (TCRs), or chimeric antigen receptors (CARs), which typically recognize native cell-surface antigens. Considerable progress has been made in recent years to address the challenges posed by the transfer of either receptor type. Vector and protein modifications enable the expression of TCR chains in human T cells at functional levels and with a reduced risk of mis-pairing with endogenous TCR chains. The combinatorial inclusion of activating and costimulatory domains in CARs has dramatically enhanced the signaling properties of the chimeric receptors described over a decade ago. Based on the effective T-cell transduction and expansion procedures now available to support clinical investigation, improved designer TCRs and second generation CARs targeting an array of antigens are being evaluated in a range of hematological malignancies and solid tumors.

From the Molecular Pharmacology and Chemistry Program, Center for Cell Engineering, Memorial Sloan-Kettering Cancer Center, New York, NY.

Reprints: Michel Sadelain, MD, PhD, Center for Cell Engineering, Box 182, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065. E-mail: m-sadelain@ski.mskcc.org.

© 2009 Lippincott Williams & Wilkins, Inc.