Intercellular adhesion molecule‐1‐targeted near‐infrared photoimmunotherapy of triple‐negative breast cancer

• Published in: Cancer science 2022-09, Vol.113 (9), p.3180-3192
• Main Authors: Fukushima, Hiroshi, Kato, Takuya, Furusawa, Aki, Okada, Ryuhei, Wakiyama, Hiroaki, Furumoto, Hideyuki, Okuyama, Shuhei, Kondo, Eisaku, Choyke, Peter L., Kobayashi, Hisataka
• Format: Article
• Language: English
• Subjects: Actin; Animal models; Antigens; Breast cancer; cancer; Cancer therapies; Cell adhesion; Cell adhesion & migration; Cell adhesion molecules; Cell membranes; Cell surface; Chemotherapy; Cloning; cytoplasmic degeneration; Cytoskeleton; Degeneration; Epidermal growth factor; ICAM‐1; Lasers; Light; near‐infrared photoimmunotherapy; Original; ORIGINAL ARTICLES; triple‐negative breast cancer; Tumors; Xenografts
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.15466

Triple‐negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and conventional chemotherapy and molecular‐targeted therapies show limited efficacy. Near‐infrared photoimmunotherapy (NIR‐PIT) is a new anticancer treatment that selectively damages the cell membrane of cancer cells based on NIR light‐induced photochemical reactions of the antibody (Ab)‐photoabsorber (IRDye700Dx) conjugate and the cell membrane. TNBC is known to express several adhesion molecules on the cell surface providing a potential new target for therapy. Here, we investigated the therapeutic efficacy of intercellular adhesion molecule‐1 (ICAM‐1)‐targeted NIR‐PIT using xenograft mouse models subcutaneously inoculated with two human ICAM‐1‐expressing TNBC cell lines, MDAMB468‐luc and MDAMB231 cells. In vitro ICAM‐1‐targeted NIR‐PIT damaged both cell types in a NIR light dose‐dependent manner. In vivo ICAM‐1‐targeted NIR‐PIT in both models showed early histological signs of cancer cell damage, such as cytoplasmic vacuolation. Even among the cancer cells that appeared to be morphologically intact within 2 h post treatment, abnormal distribution of the actin cytoskeleton and a significant decrease in Ki‐67 positivity were observed, indicating widespread cellular injury reflected in cytoplasmic degeneration. Such damage to cancer cells by NIR‐PIT significantly inhibited subsequent tumor growth and improved survival. This study suggests that ICAM‐1‐targeted NIR‐PIT could have potential clinical application in the treatment of TNBC. Early histological changes after in vivo ICAM‐1‐targeted NIR‐PIT.