On May 16, 2022 Phio Pharmaceuticals Corp. (Nasdaq: PHIO), a clinical stage biotechnology company developing the next generation of therapeutics based on its proprietary self-delivering RNAi (INTASYL) therapeutic platform, reported new preclinical data showing that silencing BRD4 with PH-894, a self-delivering RNAi INTASYL compound, can be used to improve the characteristics of CAR-T cell products during the activation and expansion phases of the cell manufacturing process (Press release, Phio Pharmaceuticals, MAY 16, 2022, View Source [SID1234614662]). These new data will be presented at the American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 25th Annual Meeting, which is being held in Washington D.C., from May 16-19, 2022.
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"Hurdles that are faced with current CAR T-cell therapy treatment for solid tumors include cell persistence and cell exhaustion. Due to the immunosuppressive environment of the tumor, CAR T-cells may become exhausted, thereby limiting the efficacy of treatment for cancer patients," said Dr. Simon Fricker, Phio’s VP of Research and Development. "These data demonstrate that PH-894 could enhance the activity of CAR-T cells by improving the quality of the final CAR-T cell product by overcoming immunosuppression, reversing exhaustion, and preserving a phenotype associated with cell persistence. There is potential for PH-894 to play a role in boosting the potency of the next generation of CAR-T cell products to enhance adoptive cell therapy for solid tumors without using genetic manipulation."
Data from the studies conducted assessed the potential of PH-894 to improve the quality and potency of HER2-targeted CAR-T cells in a CAR-T expansion model. CAR-T cells were activated with an OKT3 antibody and treated with PH-894. Results showed that PH-894 reduced the expansion-associated production of BRD4 and BRD4-regulated genes and mitigated the production of inhibitory receptors and markers of T cell exhaustion, PD-1, TIGIT and TIM3. Additionally, PH-894 preserved putative T cell stem-cell memory and central memory, phenotypes associated with cell persistence, on HER2-CAR-T cells that were otherwise depleted by cell expansion without the use of PH-894.
Phio’s presentation detailing the data presented at ASGCT (Free ASGCT Whitepaper) titled, "Self-delivering RNAi Targeting BRD4 (PH-894) Improves the Phenotype of HER2-CAR-T Cells During Expansion" will be made available on the "Investors – Events and Presentations" section of the Company’s website (click here).