Journal
CANCER JOURNAL
Volume 20, Issue 2, Pages 160-165Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/PPO.0000000000000040
Keywords
T-cell therapies; cancer immunotherapy; CD19; CAR therapies
Categories
Funding
- National Heart, Lung, and Blood Institute (NHLBI) [T32 GM007739-31S1]
- DOD PCTA [PC101964]
- ACGT
- CRI
- DOD
- NCI
- Stand-Up to Cancer/AACR
- V Foundation
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T-cell therapies using engineered T cells show great promise for cancer immunotherapy, as illustrated by the CD19 paradigm. Much of the excitement about this approach, and second-generation CARs in particular, is due to the dramatic clinical results recently reported by a few centers, especially in acute lymphoblastic leukemia, and the applicability of this approach, in principle, to a wide range of cancers. Extending the use of CAR therapies to cancers other than B-cell malignancies will require selective tumor targeting with minimal or acceptable on-target, off-tumor effects. The identification of new CAR target antigens is thus one of the next big challenges to address. Recognizing the paucity of currently available tumor-specific targets, we have developed broadly applicable approaches to enhance the tumor selectivity and safety of engineered T cells. Here, we review 2 promising concepts. One is to improve tumor targeting based on combinatorial antigen recognition. The other uses receptors that provide antigen-specific inhibition, which we named iCARs, to divert T cells from the normal tissues one wants to protect.
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