Journal article

IL-15 Preconditioning Augments CAR T Cell Responses to Checkpoint Blockade for Improved Treatment of Solid Tumors

Lauren Giuffrida, Kevin Sek, Melissa A Henderson, Imran G House, Junyun Lai, Amanda XY Chen, Kirsten L Todd, Emma Petley, Sherly Mardiana, Izabela Todorovski, Emily Gruber, Madison J Kelly, Benjamin J Solomon, Stephin J Vervoort, Ricky W Johnstone, Ian A Parish, Paul J Neeson, Lev M Kats, Phillip K Darcy, Paul A Beavis

MOLECULAR THERAPY | CELL PRESS | Published : 2020

Abstract

Chimeric antigen receptor (CAR) T cell therapy has been highly successful in hematological malignancies leading to their US Food and Drug Administration (FDA) approval. However, the efficacy of CAR T cells in solid tumors is limited by tumor-induced immunosuppression, leading to the development of combination approaches, such as adjuvant programmed cell death 1 (PD-1) blockade. Current FDA-approved methods for generating CAR T cells utilize either anti-CD3 and interleukin (IL)-2 or anti-CD3/CD28 beads, which can generate a T cell product with an effector/exhausted phenotype. Whereas different cytokine preconditioning milieu, such as IL-7/IL-15, have been shown to promote T cell engraftment, ..

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Grants

Awarded by National Health and Medical Research Council (NHMRC)


Awarded by National Breast Cancer Foundation


Awarded by NHMRC Senior Research Fellowship


Funding Acknowledgements

The authors would like to acknowledge the assistance from the staff of the Animal Facility, Flow Cytometry Facility, and Molecular Genomics Core at the Peter MacCallum Cancer Centre. This study was funded by the National Health and Medical Research Council (NHMRC; grant numbers 1132373 and 1122444). P.A.B. is supported by a National Breast Cancer Foundation Fellowship (ID number ECF-17-005). P.K.D. is supported by an NHMRC Senior Research Fellowship (APP1136680).