Simultaneously Combined Cancer Cell- and CTLA4-Targeted NIR-PIT Causes a Synergistic Treatment Effect in Syngeneic Mouse Models

• Published in: Molecular cancer therapeutics Vol. 20; no. 11; pp. 2262 - 2273
• Main Authors: Kato, Takuya, Okada, Ryuhei, Furusawa, Aki, Inagaki, Fuyuki, Wakiyama, Hiroaki, Furumoto, Hideyuki, Okuyama, Shuhei, Fukushima, Hiroshi, Choyke, Peter L, Kobayashi, Hisataka
• Format: Journal Article
• Language: English
• Published: United States 01.11.2021
• Subjects: Animals; Cell Line, Tumor; CTLA-4 Antigen - metabolism; Disease Models, Animal; Female; Immunoconjugates - pharmacology; Immunoconjugates - therapeutic use; Immunotherapy - methods; Mice; Molecular Targeted Therapy - methods
• ISSN: 1535-7163; 1538-8514
• DOI: 10.1158/1535-7163.mct-21-0470

Near-infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that utilizes antibody-IRDye700DX (IR700) conjugates. The clinical use of NIR-PIT has recently been approved in Japan for patients with inoperable head and neck cancer targeting human epidermal growth factor receptor (hEGFR). Previously, cytotoxic T-lymphocyte antigen 4 (CTLA4)-targeted NIR-PIT has been shown to strongly inhibit tumor progression and prolonged survival was seen in different tumor models due to enhanced T-cell-mediated antitumor immunity. In this study, combined NIR-PIT targeting CTLA4 expressing cells and cancer cells was investigated in four tumor models including a newly established hEGFR-expressing murine oropharyngeal cancer cell (mEERL-hEGFR). While single molecule-targeted therapy (NIR-PIT targeting hEGFR or CTLA4) did not inhibit tumor progression in poorly immunogenic mEERL-hEGFR tumor, dual (CTLA4/hEGFR)-targeted NIR-PIT significantly suppressed tumor growth and prolonged survival resulting in a 38% complete response rate. After the dual-targeted NIR-PIT, depletion of CTLA4 expressing cells, which were mainly regulatory T cells (Tregs), and an increase in the CD8 /Treg ratio in the tumor bed were observed, suggesting enhanced host antitumor immunity. Furthermore, dual-targeted NIR-PIT showed antitumor immunity in distant untreated tumors of the same type. Thus, simultaneous cancer cell-targeted NIR-PIT and CTLA4-targeted NIR-PIT is a promising new cancer therapy strategy, especially in poorly immunogenic tumors where NIR-PIT monotherapy is suboptimal.