On September 19, 2024 Rakuten Medical, Inc., a global biotechnology company developing and commercializing precision, cell-targeting therapies based on its proprietary Alluminox platform, reported that the research results of the preclinical studies for PD-L1-targeted photoimmunotherapy were presented at the 83rd Annual Meeting of the Japanese Cancer Association (JCA2024) in Fukuoka, Japan on September 20, 2024 (JST) (Press release, Rakuten Medical, SEP 19, 2024, View Source [SID1234646755]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The key findings presented at JCA2024
Abstract Title: PD-L1 photoimmunotherapy kills immunosuppressive myeloid cells to activate local and systemic antitumor immunity
Presenter: Amy H. Thorne, Ph.D. (Rakuten Medical, Inc.)
Abstract Number: 30050

It has been observed in in vitro studies that this photoimmunotherapy has a dual mechanism of action (MoA): depletion of PD-L1 expressing tumor cells and depletion of PD-L1 expressing immunosuppressive cells such as tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs). In addition to this dual MoA, the potential for systemic immune checkpoint inhibition was also observed.
It has been observed in in vivo studies that the treatment resulted in more effective tumor growth suppression compared to anti-PD-L1 antibody alone in an anti-PD-L1 sensitive mouse tumor model and tumor growth suppression compared to saline control in an anti-PD-L1 resistant mouse tumor model.
It has been observed in in vivo studies that the treatment affects the tumor microenvironment balance by depleting immunosuppressive tumor microenvironment cells and maintains checkpoint inhibition to enhance CD8+ T cell activation.
RM-0256 was well-tolerated in a GLP toxicity study in which the drug was administered repeatedly to cynomolgus monkeys.
Based on the preclinical study data, Rakuten Medical is currently considering new clinical development opportunities.

About RM-0256
RM-0256 is a conjugate of a newly developed anti-PD-L1 antibody and IRDye700DX (IR700), a light-activatable dye, that accumulates specifically on PD-L1-expressing cells. PD-L1 is a protein that inhibits the anti-cancer immune response by deactivating killer T cells, via binding to PD-1 which is abundantly expressed on the T cell surface1. PD-L1 is expressed in many solid tumors such as melanoma, lung, urothelial, gastrointestinal, gynecological, breast, and head and neck, among others, helping these tumors evade the immune system2. In addition to being present on tumor cells, PD-L1 is also expressed on suppressive immune cells within the tumor microenvironment such as tumor associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs)3. In preclinical studies, PD-L1-targeted photoimmunotherapy resulted in the necrosis of PD-L1 expressing target cells and activation of an anti-cancer immune response. Furthermore, RM-0256 was shown to inhibit the PD-L1:PD-1 interaction, and thus is expected to act systemically as an immune checkpoint inhibitor, further enhancing the anticancer immune response after PD-L1-targeted photoimmunotherapy.