Journal article
Dual-specific chimeric antigen receptor T cells and an indirect vaccine eradicate a variety of large solid tumors in an immunocompetent, self-antigen setting
CY Slaney, B Von Scheidt, AJ Davenport, PA Beavis, JA Westwood, S Mardiana, DC Tscharke, S Ellis, HM Prince, JA Trapani, RW Johnstone, MJ Smyth, MW Teng, A Ali, Z Yu, SA Rosenberg, NP Restifo, P Neeson, PK Darcy, MH Kershaw
Clinical Cancer Research | Published : 2017
Abstract
Purpose: While adoptive transfer of T cells bearing a chimeric antigen receptor (CAR) can eliminate substantial burdens of some leukemias, the ultimate challenge remains the eradication of large solid tumors for most cancers. We aimed to develop an immunotherapy approach effective against large tumors in an immunocompetent, self-antigen preclinical mouse model. Experimental Design: In this study, we generated dual-specific T cells expressing both a CAR specific for Her2 and a TCR specific for the melanocyte protein (gp100). We used a regimen of adoptive cell transfer incorporating vaccination (ACTIV), with recombinant vaccinia virus expressing gp100, to treat a range of tumors including orth..
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Awarded by National Cancer Institute
Funding Acknowledgements
This work was supported by grants from the Cancer Council of Victoria, Australia (1066554), The Peter MacCallum Cancer Center Foundation, and the National Health and Medical Research Council (NHMRC) of Australia (1103352). C.Y. Slaney and P. Beavis were supported by Postdoctoral Fellowships from the National Breast Cancer Foundation of Australia. A.J. Davenport and S. Mardiana received Postgraduate Scholarships from the Fight Cancer Foundation and University of Melbourne respectively. R.W. Johnstone and M.J. Smyth were supported by Senior Principal Research Fellowships from the NHMRC. M.H. Kershaw and P.K. Darcy were supported by Senior Research Fellowships from the NHMRC. S. Ellis was supported by a New Investigator Grant from the NHMRC.