A cancer vaccine-mediated postoperative immunotherapy for recurrent and metastatic tumors

• Published in: Nature communications Vol. 9; no. 1; pp. 1532 - 12
• Main Authors: Wang, Tingting, Wang, Dangge, Yu, Haijun, Feng, Bing, Zhou, Fangyuan, Zhang, Hanwu, Zhou, Lei, Jiao, Shi, Li, Yaping
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 18.04.2018; Nature Publishing Group UK; Nature Portfolio
• Subjects: Animals; Anticancer properties; Antitumor activity; Cancer; Cancer vaccines; Cancer Vaccines - therapeutic use; Cytotoxicity; Dendritic cells; Dendritic Cells - cytology; Female; Humans; Hydrogels; Hydrogels - chemistry; Hydrogen - chemistry; Immune checkpoint; Immune response; Immune system; Immunity; Immunological memory; Immunotherapy; Indocyanine Green - chemistry; Infiltration; Irradiation; Lasers; Lymphocytes; Lymphocytes T; Metastases; Mice; Mice, Inbred BALB C; Neoplasm Metastasis; Neoplasm Transplantation; Neoplasms - immunology; Neoplasms - surgery; Neoplasms - therapy; NIH 3T3 Cells; PD-L1 protein; Peptides - chemistry; Postoperative Period; Recurrence; T-Lymphocytes, Cytotoxic - cytology; Tumor cells; Tumors; Vaccines
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-03915-4

Vaccines to induce effective and sustained antitumor immunity have great potential for postoperative cancer therapy. However, a robust cancer vaccine simultaneously eliciting tumor-specific immunity and abolishing immune resistance continues to be a challenge. Here we present a personalized cancer vaccine (PVAX) for postsurgical immunotherapy. PVAX is developed by encapsulating JQ1 (a BRD4 inhibitor) and indocyanine green (ICG) co-loaded tumor cells with a hydrogel matrix. Activation of PVAX by 808 nm NIR laser irradiation significantly inhibits the tumor relapse by promoting the maturation of dendritic cells and eliciting tumor infiltration of cytotoxic T lymphocytes. A mechanical study reveals that NIR light-triggered antigen release and JQ1-mediated PD-L1 checkpoint blockade cumulatively contribute to the satisfied therapeutic effect. Furthermore, PVAX prepared from the autologous tumor cells induces patient-specific memory immune response to prevent tumor recurrence and metastasis. The PVAX model might provide novel insights for postoperative immunotherapy.