Immune checkpoint inhibitors have shown promise in cancer treatment by helping the immune system recognize and attack cancer cells. However, many tumors remain resistant to these treatments. To address this challenge, Dr. Rohan Fernandes, a professor at George Washington University, developed a novel patented technology by combining Prussian Blue Nanoparticles (PBNPs) with known stimulatory CD137 antibodies to target immune cells that are resistant to immune therapy. CD137 is a TNF-receptor on T Cells, dendritic cells, and NK cells that possesses the potential to upregulate anti-tumor responses when stimulated. PBNPs photothermal properties allow them to absorb light and convert it into heat (photothermal therapy, PTT), effectively killing tumor cells (Figure. 1 A and B). When these PBNPs are combined with CD137 agonists, which stimulate the immune system, T cell activation increases and encourages an anti-tumor response through T cell cytotoxicity. This two-pronged approach of PTT and immunomodulation aims to enhance the overall anti-tumor response in tandem with the direct elimination of cells by heat generation, thus increasing the effectivity of tumor cell elimination and increasing survival in vivo (Figure. 1C).
Figure 1: PBNP-PTT generates immunogenicity of SM1 (Melanoma) cells (A) Illustration of effects of varying thermal doses of PBNP-PTT on immunogenicity, specifically in melanoma cells, by either directly killing the tumor cells or activating T cells to kill the tumor cells. (B) Demonstrates in vitro viability of tumor cells at various effective doses of PBNP-PTT. (C) Increased survival of tumor bearing mice upon treatment with PBNP-PTT + aCD137.
Publication:
Photothermal therapy co-localized with CD137 agonism improves survival in an SM1 melanoma model without hepatotoxicity. Jacob A Medina, Debbie K Ledezma , Joshua Ghofrani, Jie Chen, Samantha J Chin, Preethi Bala Balakrishnan, Norman H Lee, Elizabeth E Sweeney, Rohan Fernandes. Nanomedicine (Lond). 2024 Sep 3;19(25):2049–2064.
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