Format

Send to

Choose Destination
Cancers (Basel). 2019 Dec 1;11(12). pii: E1909. doi: 10.3390/cancers11121909.

A Novel Anti-PD-L1 Vaccine for Cancer Immunotherapy and Immunoprevention.

Author information

1
Pomona Biotechnology Corp., 605 E Huntington Drive, Monrovia, CA 91016, USA.
2
Department of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1450 Biggy St, Los Angeles, CA 90033, USA.
3
Department of Hematology and Oncology, Taipei Medical University Hospital and Department of Medicine, Taipei Medical University, Taipei 110, Taiwan.
4
Jiyan Biomedical Corp., Taipei 110, Taiwan.

Abstract

Dendritic cells (DCs) are potent antigen-presenting cells that play a critical role in activating cellular and humoral immune responses. DC-based tumor vaccines targeting tumor-associated antigens (TAAs) have been extensively tested and demonstrated to be safe and potent in inducing anti-TAA immune responses in cancer patients. Sipuleucel-T (Provenge), a cancer vaccine of autologous DCs loaded with TAA, was approved by the United States Food and Drug Administration (FDA) for the treatment of castration-resistant prostate cancer. Sipuleucel-T prolongs patient survival, but has little or no effect on clinical disease progression or biomarker kinetics. Due to the overall limited clinical efficacy of tumor vaccines, there is a need to enhance their potency. PD-L1 is a key immune checkpoint molecule and is frequently overexpressed on tumor cells to evade antitumor immune destruction. Repeated administrations of PD-L1 or PD-1 antibodies have induced sustained tumor regression in a fraction of cancer patients. In this study, we tested whether vaccinations with DCs, loaded with a PD-L1 immunogen (PDL1-Vax), are able to induce anti-PD-L1 immune responses. We found that DCs loaded with PDL1-Vax induced anti-PD-L1 antibody and T cell responses in immunized mice and that PD-L1-specific CTLs had cytolytic activities against PD-L1+ tumor cells. We demonstrated that vaccination with PDL1-Vax DCs potently inhibited the growth of PD-L1+ tumor cells. In summary, this study demonstrates for the first time the principle and feasibility of DC vaccination (PDL1-Vax) to actively induce anti-PD-L1 antibody and T cell responses capable of inhibiting PD-L1+ tumor growth. This novel anti-PD-L1 vaccination strategy could be used for cancer treatment and prevention.

KEYWORDS:

PD-L1; dendritic cells; immune checkpoint; immunotherapy; tumor vaccine

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center