Topic 371: Validation and Optimization of RP-185 as Adjuvant to Exploit the Immune Response Generated by Radiation

Radiotherapy, a key anticancer therapy, acts not only by killing cancer cells, but also by activating the body's immune system to attack the remaining cancer cells. However, the immune-stimulating effect is weakened by the tumor's capacity to reprogram immune cells, particularly macrophages, so that they instead actively promote tumor growth. RP-185 (Riptide Biosciences, Vallejo, CA),an engineered analog of a natural immunomodulatory peptide, has been shown to reverse this programming and restore the immune cells to tumor-Killing activity. This effect is additive to the T-cell sensitizing activity of checkpoint inhibitors, whose efficacy as an adjunct to radiotherapy is already being pursued in many clinical trials. we propose to confirm the efficacy and safety of RP-185 as a radiotherapy adjuvant, and establish optimum dosing schedules and concentrations preparatory to clinical trials.