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Int. J. Mol. Sci. 2019, 20(8), 1903; https://doi.org/10.3390/ijms20081903

CAR-T with License to Kill Solid Tumors in Search of a Winning Strategy

1
Department of Science, University Roma Tre, 00146 Rome, Italy
2
Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy
3
Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy
*
Author to whom correspondence should be addressed.
Received: 19 March 2019 / Revised: 11 April 2019 / Accepted: 13 April 2019 / Published: 17 April 2019
(This article belongs to the Special Issue CAR-T Cell Therapy)
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Abstract

Artificial receptors designed for adoptive immune therapies need to absolve dual functions: antigen recognition and abilities to trigger the lytic machinery of reprogrammed effector T lymphocytes. In this way, CAR-T cells deliver their cytotoxic hit to cancer cells expressing targeted tumor antigens, bypassing the limitation of HLA-restricted antigen recognition. Expanding technologies have proposed a wide repertoire of soluble and cellular “immunological weapons” to kill tumor cells; they include monoclonal antibodies recognizing tumor associated antigens on tumor cells and immune cell checkpoint inhibition receptors expressed on tumor specific T cells. Moreover, a wide range of formidable chimeric antigen receptors diversely conceived to sustain quality, strength and duration of signals delivered by engineered T cells have been designed to specifically target tumor cells while minimize off-target toxicities. The latter immunological weapons have shown distinct efficacy and outstanding palmarès in curing leukemia, but limited and durable effects for solid tumors. General experience with checkpoint inhibitors and CAR-T cell immunotherapy has identified a series of variables, weaknesses and strengths, influencing the clinical outcome of the oncologic illness. These aspects will be shortly outlined with the intent of identifying the still “missing strategy” to combat epithelial cancers. View Full-Text
Keywords: CAR-T; chimeric antigen receptors; immunotherapy; solid tumors; universal CAR; CD16-CR CAR-T; chimeric antigen receptors; immunotherapy; solid tumors; universal CAR; CD16-CR
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Sacchetti, B.; Botticelli, A.; Pierelli, L.; Nuti, M.; Alimandi, M. CAR-T with License to Kill Solid Tumors in Search of a Winning Strategy. Int. J. Mol. Sci. 2019, 20, 1903.

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