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Scientific article
Review
English

Keeping the Engine Running: The Relevance and Predictive Value of Preclinical Models for CAR-T Cell Development

Published inILAR journal, vol. 59, no. 3, p. 276-285
Publication date2018
Abstract

The cellular immunotherapy field has achieved important milestones in the last 30 years towards the treatment of a variety of cancers due to improvements in ex-vivo T cell manufacturing processes, the invention of synthetic T cell receptors, and advances in cellular engineering. Here, we discuss major preclinical models that have been useful for the validation of chimeric antigen receptor (CAR)-T cell therapies and also promising new models that will fuel future investigations towards success. However, multiple unanswered questions in the CAR-T cell field remain to be addressed that will require innovative preclinical models. Key challenges facing the field include premature immune rejection of universal CAR-T cells and the immune suppressive tumor microenvironment. Immune competent models that accurately recapitulate tumor heterogeneity, the hostile tumor microenvironment, and barriers to CAR-T cell homing, toxicity, and persistence are needed for further advancement of the field.

Keywords
  • Animals
  • Humans
  • Immunotherapy, Adoptive/methods
  • Neoplasms/therapy
  • Translational Medical Research/methods
  • Tumor Microenvironment/physiology
Citation (ISO format)
MIGLIORINI, Denis, MASON, Nicola J, POSEY, Avery D. Keeping the Engine Running: The Relevance and Predictive Value of Preclinical Models for CAR-T Cell Development. In: ILAR journal, 2018, vol. 59, n° 3, p. 276–285. doi: 10.1093/ilar/ilz009
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ISSN of the journal1084-2020
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