New strategies in engineering T-cell receptor gene-modified T cells to more effectively target malignancies

Thomas M. Schmitt, Ingunn M. Stromnes, Aude G. Chapuis, Philip D. Greenberg

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

The immune system, T cells in particular, have the ability to target and destroy malignant cells. However, antitumor immune responses induced from the endogenous T-cell repertoire are often insufficient for the eradication of established tumors, as illustrated by the failure of cancer vaccination strategies or checkpoint blockade for most tumors. Genetic modification of T cells to express a defined T-cell receptor (TCR) can provide the means to rapidly generate large numbers of tumor-reactive T cells capable of targeting tumor cells in vivo. However, cell-intrinsic factors as well as immunosuppressive factors in the tumor microenvironment can limit the function of such gene-modified T cells. New strategies currently being developed are refining and enhancing this approach, resulting in cellular therapies that more effectively target tumors and that are less susceptible to tumor immune evasion.

Original languageEnglish (US)
Pages (from-to)5191-5197
Number of pages7
JournalClinical Cancer Research
Volume21
Issue number23
DOIs
StatePublished - Dec 1 2015

Bibliographical note

Funding Information:
T.M. Schmitt is supported by the Jose Carreras International Leukemia Foundation E.D. Thomas Post-Doctoral Fellowship. I.M. Stromnes is supported by the Irvington Institute Fellowship Program of the Cancer Research Institute and the Jack Paul Estate Fund to Support Collaborative Immunotherapy Research. A.G. Chapuis is supported by the NCI of the NIH under award number K08CA169485. P.D. Greenberg is supported by the NCI of the NIH under award numbers P01CA18029 and R01CA33084, and a grant from the Korean Research Institute of Bioscience and Biotechnology.

Publisher Copyright:
© 2015 American Association for Cancer Research.

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