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Open AccessArticle

PD-1 Immune Checkpoint Blockade Promotes Therapeutic Cancer Vaccine to Eradicate Lung Cancer

by Pournima Kadam 1 and Sherven Sharma 1,2,3,*
1
Molecular Gene Medicine Laboratory, Veterans Affairs Greater Los Angeles, Healthcare System, 11301, Wilshire Blvd, Los Angeles, CA 90073, USA
2
Department of Medicine, UCLA Lung Cancer Research Program, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
3
Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
*
Author to whom correspondence should be addressed.
Vaccines 2020, 8(2), 317; https://doi.org/10.3390/vaccines8020317
Received: 20 May 2020 / Revised: 10 June 2020 / Accepted: 12 June 2020 / Published: 18 June 2020
(This article belongs to the Special Issue Cancer Vaccine)
(1) Background: Targeting inhibitory immune checkpoint molecules has highlighted the need to find approaches enabling the activation of immune responses against cancer. Therapeutic vaccination, which induces specific immune responses against tumor antigens (Ags), is an attractive option. (2) Methods: Utilizing a K-RasG12Dp53null murine lung cancer model we determined tumor burden, tumor-infiltrating T cell (TIL) cytolysis, immunohistochemistry, flow cytometry, and CD4 and CD8 depletion to evaluate the efficacy of PD-1 blockade combined with CCL21-DC tumor lysate vaccine. (3) Results: Anti-PD-1 plus CCL21-DC tumor lysate vaccine administered to mice bearing established tumors (150 mm3) increased expression of perforin and granzyme B in the tumor microenvironment (TME), increased tumor-infiltrating T cell (TIL) activity, and caused 80% tumor eradication. Mice with treatment-induced tumor eradication developed immunological memory, enabling tumor rejection upon challenge and cancer-recurrence-free survival. The depletion of CD4 or CD8 abrogated the antitumor activity of combined therapy. PD-1 blockade or CCL21-DC tumor lysate vaccine monotherapy reduced tumor burden without tumor eradication. (4) Conclusion: Immune checkpoint blockade promotes the activity of the therapeutic cancer vaccine. PD-1 blockade plus CCL21-DC tumor lysate vaccine therapy could benefit lung cancer patients. View Full-Text
Keywords: lung cancer; PD-1; immune checkpoint; CCL21; dendritic cells; immunotherapy; tumor lysate antigen lung cancer; PD-1; immune checkpoint; CCL21; dendritic cells; immunotherapy; tumor lysate antigen
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Kadam, P.; Sharma, S. PD-1 Immune Checkpoint Blockade Promotes Therapeutic Cancer Vaccine to Eradicate Lung Cancer. Vaccines 2020, 8, 317.

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