On November 9, 2019 Rakuten Medical, Inc. (RMI) a clinical-stage, global biotechnology company developing precision-targeted cancer therapies based on Rakuten Medical’s Illuminox, its proprietary, anti-cancer treatment platform, reported new preclinical data suggesting CD25 photoimmunotherapy (PIT) treatment, combined with an anti-PD1 therapy, may stimulate the immune system, and lead to a synergistic, anti-cancer activity in targeted tumors (Press release, Rakuten Medical, NOV 9, 2019, View Source [SID1234550813]).
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"These exciting data suggests that anti-CD25 photoimmunotherapy may alter the immune tumor environment and unlock the potential of combination immunotherapies for patients living with certain types of cancers for which there are few treatment options," said Miguel Garcia-Guzman, Ph.D., Vice Chairman and Chief Scientific Officer at Rakuten Medical. "We are committed to harnessing the full potential of the immune system through modulation of the cancer tumor environment, and these results support our clinical development program based on our anti-cancer treatment platform, Rakuten Medical’s Illuminox."
The preclinical data were showcased during a poster presentation during the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 34th annual meeting:
"Intratumoral depletion of regulatory T-cells using CD25 targeted photoimmunotherapy elicits anti-cancer immune activity and synergizes with PD1 checkpoint blockade in immunocompetent mouse models." (Abstract P774), presented by Jerry J. Fong, Cancer Biology and Pharmacology, Rakuten Medical.
The poster discusses intratumoral depletion of regulatory T-cells (Tregs), a significant source of immune suppression, with an anti-CD25-IR700 conjugate therapy using PIT. Anti-cancer activity and subsequent immune responses following anti-CD25-IR700 PIT treatment, administered alone or in combination with anti-PD1 treatment, were evaluated in immunocompetent mouse models. Key highlights from the studies include:
Rapid and significant reduction of intratumoral Tregs, eliciting significant anti-cancer activity
An increase of non-exhausted T-cells following a single treatment, suggesting systemic activation and intratumoral recruitment of new CD8 T-cells from the periphery
Significant enhancement of anti-cancer activity in vivo, as demonstrated by percentage of mice achieving complete responses (CRs) with combination treatment in comparison to animals receiving one treatment alone
Durable increase of intratumoral CD8 T-cell/Treg ratio
Enhanced systemic adaptive immune responses and induced abscopal anti-cancer effects in a CD8 T-cell dependent manner
Tumor-specific immune memory response as demonstrated by systemic tumor-antigen-specific cytotoxic lymphocytes expansion and prevention of new tumor growth in CR mice
Combination treatment enhanced systemic adaptive immune responses and induced abscopal anti-cancer effects in a CD8 T-cell dependent manner