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Immune Checkpoint Blockade Enhances Immune Activity of Therapeutic Lung Cancer Vaccine

Pournima Kadam¹, Ram P Singh¹, Michael Davoodi¹

¹Department of Medicine, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA.

|November 10, 2020

Abstract

Background:

Immune checkpoint blockade that downregulates T cell evasion for effective immunity has provided a renewed interest in therapeutic cancer vaccines.

Methods:

Utilizing murine lung cancer models, we determined: tumor burden, TIL cytolysis, immunohistochemistry, flow cytometry, RNA Sequencing, CD4 T cells, CD8 T cells, CXCL9 chemokine, and CXCL10 chemokine neutralization to evaluate the efficacy of Programmed cell death protein 1 (PD-1) blockade combined with chemokine (C-C motif) ligand 21-dendritic cell tumor antigen (CCL21-DC tumor Ag) vaccine.

Results:

Anti-PD1 combined with CCL21-DC tumor Ag vaccine eradicated 75% of 12-day established tumors (150 mm³) that was enhanced to 90% by administering CCL21-DC tumor Ag vaccine prior to combined therapy. The effect of combined therapy was blocked by CD4, CD8, CXCL9, and CXCL10 neutralizing antibodies.

Conclusion:

PD-1 blockade therapy plus CCL21-DC tumor Ag vaccine could be beneficial to lung cancer patients.

Keywords:

CCL21 PD-1 T cells dendritic cells (DC)lung cancer tumor microenvironment (TME)

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