[Frontiers in Bioscience S4, 520-531, January 1, 2012]

[Frontiers in Bioscience S4, 520-531, January 1, 2012]

Chimeric antibody receptors (CARs): Driving T-cell specificity to enhance anti-tumor immunity

Partow Kebriaei¹, Susan S. Kelly², Pallavi Manuri², Bipulendu Jena², Rineka Jackson², Elizabeth Shpall¹, Richard Champlin¹, Laurence J. N. Cooper²

1Division of Cancer Medicine and ²Division of Pediatrics, University of Texas MD Anderson Cancer Center, Houston, Texas

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. CAR structure
4. Approaches to genetic modification of T cells to express CAR
5. Improved persistence of CAR+ T cells
6. Improved trafficking of CAR+ T cells
7. Non-invasive imaging of CAR+ T cells
8. Safety of CAR+ T cells
9. Future directions of CARs
10. Acknowledgments
11. References

1. ABSTRACT

Adoptive transfer of antigen-specific T cells is a compelling tool to treat cancer. To overcome issues of immune tolerance which limits the endogenous adaptive immune response to tumor-associated antigens, robust systems for the geneticmodification and characterization of T cells expressing chimeric antigen receptors (CARs) to redirect specificity have been produced. Refinements with regards to persistence and trafficking of the genetically modified T cells are underway to help improve the potency of genetically modified T cells. Clinical trials utilizing this technology demonstrate feasibility, and increasingly, antitumor activity, paving the way for multi-center trials to establish the efficacy of this novel T-cell therapy.