Journal article

An ultrastructural investigation of tumors undergoing regression mediated by immunotherapy

Jennifer A Westwood, Sarah Ellis, Jill Danne, Chad Johnson, Viola Oorschot, Georg Ramm, David C Tscharke, Alexander J Davenport, James C Whisstock, Phillip K Darcy, Michael H Kershaw, Clare Y Slaney

ONCOTARGET | IMPACT JOURNALS LLC | Published : 2017

Abstract

While immunotherapy employing chimeric antigen receptor (CAR) T cells can be effective against a variety of tumor types, little is known about what happens within the tumor at an ultrastructural level during tumor regression. Here, we used transmission electron microscopy to investigate morphologic and cellular features of tumors responding to immunotherapy composed of adoptive transfer of dual-specific CAR T cells and a vaccine, supported by preconditioning irradiation and interleukin-2. Tumors responded rapidly, and large areas of cell death were apparent by 4 days after treatment. The pleomorphic and metabolically active nature of tumor cells and phagocytic activity of macrophages were ap..

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Grants

Awarded by Cancer Council of Victoria, Australia


Awarded by Cancer Australia and Cure Cancer Australia


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


Awarded by National Breast Cancer Foundation of Australia


Awarded by Susan G. Komen Breast Cancer Foundation


Awarded by National Breast Cancer Foundation


Funding Acknowledgements

This work was supported by grants from the Cancer Council of Victoria, Australia (1066554), Cancer Australia and Cure Cancer Australia (1100199) and the National Health and Medical Research Council (NHMRC) of Australia (1103352). CYS was supported by a Postdoctoral Fellowship from the National Breast Cancer Foundation of Australia (ECF-16-005) and a Career Catalyst Award from the Susan G. Komen Breast Cancer Foundation (CCR16376637). MHK, DCT and PKD were supported by Senior Research Fellowships from the NHMRC.