Journal article

Enterotoxins can support CAR T cells against solid tumors

Bianca von Scheidt, Minyu Wang, Amanda J Oliver, Jack D Chan, Metta K Jana, Aesha I Ali, Fiona Clow, John D Fraser, Kylie M Quinn, Phillip K Darcy, Michael H Kershaw, Clare Y Slaney

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | NATL ACAD SCIENCES | Published : 2019

Abstract

Responses of solid tumors to chimeric antigen receptor (CAR) T cell therapy are often minimal. This is potentially due to a lack of sustained activation and proliferation of CAR T cells when encountering antigen in a profoundly immunosuppressive tumor microenvironment. In this study, we investigate if inducing an interaction between CAR T cells and antigen-presenting cells (APCs) in lymphoid tissue, away from an immunosuppressive microenvironment, could enhance solid-tumor responses. We combined CAR T cell transfer with the bacterial enterotoxin staphylococcal enterotoxin-B (SEB), which naturally links a proportion of T cell receptor (TCR) Vβ subtypes to MHC-II, present on APCs. CAR T cell p..

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Grants

Awarded by Cure Cancer Australia


Awarded by National Health and Medical Research Council (NHMRC) of Australia


Awarded by National Breast Cancer Foundation (NBCF) of Australia


Awarded by Susan G. Komen Breast Cancer Foundation


Funding Acknowledgements

This work was supported by grants from Cure Cancer Australia (1100199), the Peter MacCallum Cancer Center Foundation, the National Health and Medical Research Council (NHMRC) of Australia (1103352 and 1132373), the National Breast Cancer Foundation (NBCF) of Australia (IIRS-18-064), and the Susan G. Komen Breast Cancer Foundation (16376637). P.K.D. and M.H.K. were supported by NHMRC Senior Research Fellowships. C.Y.S. was supported by a Postdoctoral Fellowship from the NBCF.