Tumor control via targeting PD-L1 with chimeric antigen receptor modified NK cells

Robbins, Y.; Greene, S.; Friedman, J.; Clavijo, P. E.; Van Waes, C.; Fabian, K. P.; Padget, M. R.; Abdul Sater, H.; Lee, J. H.; Soon-Shiong, P.; Gulley, J.; Schlom, J.; Hodge, J.; Allen, C.

doi:10.1101/2020.01.30.926535

bioRxiv · 10.1101/2020.01.30.926535

Tumor control via targeting PD-L1 with chimeric antigen receptor modified NK cells

Robbins, Y.·Greene, S.·Friedman, J.·Clavijo, P. E.·Van Waes, C.·Fabian, K. P.·Padget, M. R.·Abdul Sater, H.·Lee, J. H.·Soon-Shiong, P.·Gulley, J.·Schlom, J.·Hodge, J.·Allen, C.

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Abstract

Failed T cell-based immunotherapies in the presence of genomic alterations in antigen presentations pathways may be overcome by NK cell-based immunotherapy. This approach may still be limited by the presence of immunosuppressive myeloid populations. Here we demonstrate that NK cells (haNKs) engineered to express a PD-L1 chimeric antigen receptor (CAR) haNKs killed a panel of human and murine head and neck cancer cells at low effector-to-target ratios in a PD-L1-dependent fashion. Treatment of syngeneic tumors resulted in CD8 and PD-L1-dependent tumor rejection or growth inhibition and a reduction in myeloid cells endogenously expressing high levels of PD-L1. Treatment of xenograft tumors resulted in PD-L1 dependent tumor growth inhibition. PD-L1 CAR haNKs reduced levels of macrophages and other myeloid cells endogenously expressing high PD-L1 in peripheral blood from patients with head and neck cancer. The clinical study of PD-L1 CAR haNKs is warranted.

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Robbins, Y., Greene, S., Friedman, J., Clavijo, P. E., Van Waes, C., Fabian, K. P., Padget, M. R., Abdul Sater, H., Lee, J. H., Soon-Shiong, P., Gulley, J., Schlom, J., Hodge, J., Allen, C.. 2020-01-30. Tumor control via targeting PD-L1 with chimeric antigen receptor modified NK cells. https://doi.org/10.1101/2020.01.30.926535

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