Abstract
Near infrared photoimmunotherapy (NIR-PIT) is a newly developed and highly selective cancer treatment that induces necrotic/immunogenic cell death. It employs a monoclonal antibody (mAb) conjugated to a photo-absorber dye, IRDye700DX, which is activated by NIR light. Tumor-targeting NIR-PIT is also at least partly mediated by a profound immune response against the tumor. Cytotoxic T-lymphocyte antigen-4 (CTLA4) is widely recognized as a major immune checkpoint protein, which inhibits the immune response against tumors and is therefore, a target for systemic blockade. We investigated the effect of combining tumor-targeted NIR-PIT against the cell-surface antigen, CD44, which is known as a cancer stem cell marker, with a systemic CTLA4 immune checkpoint inhibitor in three syngeneic tumor models (MC38-luc, LL/2, and MOC1). CD44-targeted NIR-PIT combined with CTLA4 blockade showed greater tumor growth inhibition with longer survival compared with CTLA4 blockade alone in all tumor models. NIR-PIT and CTLA4 blockade produced more complete remission in MOC1 tumors (44%) than NIR-PIT and programmed cell death protein 1 (PD-1) blockade (8%), which was reported in our previous paper. However, the combination of NIR-PIT and CTLA4 blockade was less effective in MC38-luc tumors (11%) than the combination of NIR-PIT and PD-1 blockade (70%). Nonetheless, in many cases ineffective results with NIR-PIT and PD-1 blockade were reversed with NIR-PIT and CTLA4 blockade.
Highlights
Near infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer treatment that induces highly specific cell death in targeted tumor cells
The purpose of this study was to investigate the in vivo therapeutic efficacy of the combination of CD44-targeted NIR-PIT and Cytotoxic T-lymphocyte antigen-4 (CTLA4) blockade in several syngeneic mouse models of cancer
Based on incorporation of propidium iodide (PI), the percentage of cell death increased in a light dose dependent manner in MC38-luc, LL/2, and MOC1 cells (Figure 1C–E)
Summary
Near infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer treatment that induces highly specific cell death in targeted tumor cells. It employs a monoclonal antibody (mAb) conjugated to a silica-phthalocyanine photoabsorbing dye, IRDye700DX (IR700) [1,2]. This antibody-IR700 conjugate is administered intravenously, and after a suitable time to allow for target binding, the tumor is exposed to 690 nm NIR light which activates IR700 [3]. A phase III clinical trial of NIR-PIT using the epidermal growth factor receptor (EGFR) -targeted antibody-IR700 conjugate, Vaccines 2020, 8, 0528; doi:10.3390/vaccines8030528 www.mdpi.com/journal/vaccines
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have