title: Combined adjuvants of poly(I:C) plus LAG-3-Ig improve antitumor effects of tumor-specific T cells, preventing their exhaustion.
abstract: Therapeutic cancer vaccines are designed to treat cancer by boosting the endogenous immune system to fight against the cancer. In the development of clinically effective cancer vaccines, one of the most practical objectives is to identify adjuvants that are capable of optimizing the vaccine effects. In this study, we explored the potential of polyinosinic-polycytidylic acid (poly(I:C)) and LAG-3-Ig (soluble recombinant protein of lymphocyte activation gene-3 [LAG-3] extracellular domain fused with human IgG Fc region) as adjuvants for P1A tumor antigen peptide vaccine in a pre-established P815 mouse tumor model with a transfer of tumor-specific T cells. Whereas the use of poly(I:C) or LAG-3-Ig as a signal adjuvant induced a slight enhancement of P1A vaccine effects compared to incomplete Freund's adjuvant, combined treatment with poly(I:C) plus LAG-3-Ig remarkably potentiated antitumor effects, leading to complete rejection of pre-established tumor and long-term survival of mice. The potent adjuvant effects of poly(I:C) plus LAG-3-Ig were associated with an enhanced infiltration of T cells in the tumor tissues, and an increased proliferation and Th1-type cytokine production of tumor-reactive T cells. Importantly, the combined adjuvant of poly(I:C) plus LAG-3-Ig downregulated expressions of PD-1, LAG-3, and TIGIT on P1A-specific T cells, indicating prevention of T cell exhaustion. Taken together, the results of the current study show that the combined adjuvants of poly(I:C) plus LAG-3-Ig with tumor peptide vaccine induce profound antitumor effects by activating tumor-specific T cells.
authors.affiliation: Department of Immunology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kano
authors.affiliation: Department of Immunology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Iguchi
authors.affiliation: Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Matsui
authors.affiliation: Department of Immunology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Keishi
authors.initials: K
authors.lastname: Adachi
authors.affiliation: Department of Immunology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Yukimi
authors.initials: Y
authors.lastname: Sakoda
authors.affiliation: NEC Corporation, Tokyo, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Miyakawa
authors.affiliation: NEC Corporation, Tokyo, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Doi
authors.affiliation: Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Hazama
authors.affiliation: Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nagano
authors.affiliation: Department of Oral and Maxillofacial Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Ueyama
authors.affiliation: Department of Immunology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Tamada
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D015703:Antigens, CD / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D019496:Cancer Vaccines / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D011070:Poly I-C / Q000008:administration & dosage* / Q000276:immunology; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D019496:Cancer Vaccines; D007074:Immunoglobulin G; D011070:Poly I-C; D000093322:Lymphocyte Activation Gene 3 Protein
keywords: Adjuvants; LAG-3; T cell exhaustion; cancer vaccine; poly(I:C)