CD29 targeted near-infrared photoimmunotherapy (NIR-PIT) in the treatment of a pigmented melanoma model. (31st December 2022)

• Record Type: Journal Article
• Authors: Furusawa, Aki; Okada, Ryuhei; Inagaki, Fuyuki; Wakiyama, Hiroaki; Kato, Takuya; Furumoto, Hideyuki; Fukushima, Hiroshi; Okuyama, Shuhei; Choyke, Peter L.; Kobayashi, Hisataka
• Is Part Of: Oncoimmunology. Volume 11:Number 1(2022)
• Publication Date: 2022-12-31
• Subjects: Cancer -- near-infrared photoimmunotherapy (NIR-PIT) -- target molecule -- melanoma -- CD29; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2021.2019922
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer treatment that utilizes an antibody-photoabsorber-conjugate (AbPC) combined with NIR light. The AbPC is injected and binds to the tumor whereupon NIR light irradiation causes a photochemical reaction that selectively kills cancer cells. NIR-PIT is ideal for surface-located skin cancers such as melanoma. However, there is concern that the pigment in melanoma lesions could interfere with light delivery, rendering treatment ineffective. We investigated the efficacy of CD29- and CD44-targeted NIR-PIT (CD29-PIT and CD44-PIT, respectively) in the B16 melanoma model, which is highly pigmented. While CD29-PIT and CD44-PIT killed B16 cells in vitro and in vivo, CD29-PIT suppressed tumor growth more efficiently. Ki67 expression showed that cells surviving CD29-PIT were less proliferative, suggesting that CD29-PIT was selective for more proliferative cancer cells. CD29-PIT did not kill immune cells, whereas CD44-PIT killed both T and NK cells and most myeloid cells, including DCs, which could interfere with the immune response to NIR-PIT. The addition of anti-CTLA4 antibody immune checkpoint inhibitor (ICI) to CD29-PIT increased the infiltration of CD8 T cells and enhanced tumor suppression with prolonged survival. Such effects were less prominent when the anti-CTLA4 ICI was combined with CD44-PIT. The preservation of immune cells in the tumor microenvironment (TME) after CD29-PIT likely led to a better response when combined with anti-CTLA4 treatment. We conclude that NIR-PIT can be performed in pigmented melanomas and that CD29 is a promising target for NIR-PIT, which is amenable to combination therapy with other immunotherapies.