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Local Depletion of Immune Checkpoint Ligand CTLA4 Expressing Cells in Tumor Beds Enhances Antitumor Host Immunity
Author(s) -
Okada Ryuhei,
Kato Takuya,
Furusawa Aki,
Inagaki Fuyuki,
Wakiyama Hiroaki,
Choyke Peter L.,
Kobayashi Hisataka
Publication year - 2021
Publication title -
advanced therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
0ISSN - 2366-3987
DOI - 10.1002/adtp.202000269
Subject(s) - cytotoxic t cell , immune system , cancer research , immune checkpoint , cancer immunotherapy , immunotherapy , tumor microenvironment , cd8 , antigen , biology , immunology , in vitro , biochemistry
Near‐infrared photoimmunotherapy (NIR‐PIT) is a cancer treatment that utilizes antibody‐photoabsorber (IR700) conjugates to selectively kill target cells by exposing them to NIR light. Cytotoxic T‐lymphocyte antigen 4 (CTLA4) is a major immune checkpoint ligand mediating antitumor immune suppression. Local depletion of CTLA4 expressing cells in the tumor bed with NIR‐PIT could enhance antitumor immune responses by both blocking the CTLA4‐axis and depleting immune suppressive cells. The aim of this study is to evaluate the antitumor efficacy of CTLA4‐targeted NIR‐PIT using four murine tumor models, MC38‐luc, LL/2‐luc, MOC2‐luc, and MOC2. The CTLA4‐targeted NIR‐PIT depletes intratumoral CTLA4 expressing cells which are mostly regulatory T cells. In vivo CTLA4‐targeted NIR‐PIT yields complete responses in 80% of MC38‐luc, 70% of LL/2‐luc, and 40% of MOC2‐luc tumors prolonging survival in all cases. After CTLA4‐targeted NIR‐PIT, activation and infiltration of CD8 + T cells within the tumor microenvironment is observed. In conclusion, CTLA4‐targeted NIR‐PIT can effectively treat tumors by blocking the CTLA4‐axis as well as by eliminating CTLA4‐expressing immune suppressor cells, resulting in T cell mediated antitumor immunity. Local CTLA4‐expressing cell depletion in tumor beds using NIR‐PIT could be a promising new cancer immunotherapy for safely treating a variety of tumor types.