thiarabine (4-thio Ara-C) / Abeona Therap - LARVOL DELTA

SRI-41302 in combination with Anti-PD-1 Antibody Induces a Memory Response in MC-38 Colon Adenocarcinoma (EACR 2024) - "Tumor resection is the standard-of-care for localized disease, with combination chemotherapy/surgery therapy for metastatic cases typically involving fluorouracil-based chemotherapies. The mechanism of action of Thiarabine is poorly understood and while it closely resembles the function of Cytarabine, not much can be attributed to its potency of the compound past the metabolic changes to the compound itself. Based on previous FDA allowances for the use of the Keytruda checkpoint inhibitor in the presence of MSS or chronic MSI, regardless of PD1/PDL1 status, we devised a series of in vitro and in vivo experiments to determine if nucleosides could perturb an otherwise inert tumor environment such that an immune response would be mounted to induced DNA damage."

Combination therapy • IO biomarker • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Microsatellite Instability • Oncology • MSI

Efficacy of three checkpoint Inhibitors, five chemotherapeutic agents, and the experimental drug thiarabine against MC38 colon cancer expressing human PD-L1 in transgenic C57BL/6 mice expressing human PD-1 and PD-L1 checkpoint genes (AACR 2019) - "...Growth inhibition was 84%, 58%, and 94% on Day 17 for nivolumab, atezolizumab, and pembrolizumab, respectively, compared to the control animals...To prepare for combination studies, we also tested cisplatin, irinotecan, gemcitabine, decitabine, rucaparib, and thiarabine near the MTD for each agent with various treatment schedules against the established tumors...We have shown that PD-1 inhibitors are effective in treating genetically modified MC38 colon tumors in transgenic mice in early treatment and in established tumors while the PD-L1 inhibitor was only effective in early treatment. We also have identified doses and schedules of five chemotherapeutic agents to use in future combination studies in this model."

Checkpoint inhibition