Journal Article

Near‐infrared photoimmunotherapy targeting PD‐L1: Improved efficacy by preconditioning the tumor microenvironment

Inagaki, Fuyuki F., Fukushima, Hiroshi, Furusawa, Aki, Kato, Takuya, Kano, Makoto, Okada, Ryuhei, Choyke, Peter L., Kobayashi, Hisataka, Takao, Seiichiro, Okuyama, Shuhei

2024

Overview

Near‐infrared photoimmunotherapy (NIR‐PIT) is a new type of cancer therapy that employs antibody‐IRDye700DX conjugates (AbPCs) and near‐infrared (NIR) light at a wavelength of 689 nm, the excitation wavelength of IR700. Administered intravenously, injected AbPCs bind specifically to cells expressing the target antigen, whereupon NIR light exposure causes rapid, selective killing. This process induces an anticancer T cell response, leading to sustained anticancer host immune response. Programmed cell death ligand‐1 (PD‐L1) is a major inhibitory immune checkpoint molecule expressed in various cancers. In this study, we first assessed the efficacy of PD‐L1‐targeted NIR‐PIT (αPD‐L1‐PIT) in immune‐competent tumor mouse models. αPD‐L1‐PIT showed a significant therapeutic effect on the tumor models with high PD‐L1 expression. Furthermore, αPD‐L1‐PIT induced an abscopal effect on distant tumors and long‐term immunological memory. In contrast, αPD‐L1‐PIT was not as effective for tumor models with low PD‐L1 expression. To improve the efficacy of PD‐L1‐targeted NIR‐PIT, PEGylated interferon‐gamma (IFNγ) was administered with αPD‐L1‐PIT. The combination therapy improved the treatment efficacy by increasing PD‐L1 expression leading to more efficient cell killing by αPD‐L1‐PIT. Furthermore, the PEGylated IFNγ led to a CD8+ T cell‐dominant tumor microenvironment (TME) with an enhanced anticancer T cell response after αPD‐L1‐PIT. As a result, even so‐called cold tumors exhibited complete responses after αPD‐L1‐PIT. Thus, combination therapy of PEGylated IFNγ and PD‐L1‐targeted NIR‐PIT has the potential to be an important future strategy for cancer immunotherapy. The combination therapy improved the treatment efficacy by increasing programmed cell death ligand‐1 (PD‐L1) expression leading to more efficient cell killing by anti‐PD‐L1 antibody photoimmunotherapy (αPD‐L1‐PIT). Furthermore, the PEGylated interferon‐gamma (IFNγ) led to a CD8+ T cell‐dominant tumor microenvironment (TME) with an enhanced anticancer T cell response after αPD‐L1‐PIT. As a result, even so‐called cold tumors exhibited complete responses after αPD‐L1‐PIT. Thus, combination therapy of PEGylated IFNγ and PD‐L1‐targeted near‐infrared (NIR)‐PIT has the potential to be an important future strategy for cancer immunotherapy.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Animal models / Animals / Antibodies / Antigens / Apoptosis / B7-H1 Antigen - antagonists & inhibitors / B7-H1 Antigen - immunology / B7-H1 Antigen - metabolism / Cancer immunotherapy / Cancer therapies / CD8 antigen / Cell death / Cell Line, Tumor / Clinical trials / Female / Flow cytometry / Humans / I.R. radiation / Immune checkpoint / immune checkpoint inhibitor / Immunoconjugates - pharmacology / Immunoconjugates - therapeutic use / Immunological memory / Immunotherapy - methods / Indoles - pharmacology / Indoles - therapeutic use / Infrared Rays / interferon‐gamma / Ligands / Light / Lymphocytes / Lymphocytes T / Mice / Mice, Inbred C57BL / near‐infrared photoimmunotherapy / Oral cancer / Original / ORIGINAL ARTICLE / PD-L1 protein / PD‐L1 / Pharmacokinetics / Phototherapy - methods / Tumor microenvironment / Tumor Microenvironment - drug effects / Tumor Microenvironment - immunology / Tumors / Wavelength / γ-Interferon