Mechanism of Action and Clinical Overview of Imprime PGG(R)-A Novel Neutrophil-enhancing Anti-tumor

来源 :BITs 3rd Annual World Cancer Congress-2012(2012第五届世界癌症大会) | 被引量 : 0次 | 上传用户:C07467001
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  Imprime PGG(R) Injection (Imprime PGG) is an immunomodulatory beta-glucan polymer isolated from a proprietary stain of Saccharomyces cerevisiae that selectively binds to complement receptor 3 (CR3) on neutrophils and enables this largest population of immune cells in the body to kill tumor cells tagged with monoclonal antibodies (Mabs).Synergy between Imprime PGG and tumor-targeting Mabs in reducing tumor growth and enhancing long-term survival has been demonstrated in over a dozen murine tumor models involving different tumors and different Mabs.In vivo knock-out animal studies have demonstrated that the effects of Imprime PGG require the presence of complement ?, CR3 on the immune cells, and the presence of neutrophils.Three studies with Imprime PGG in healthy volunteer subjects have demonstrated a good tolerability and safety profile and Imprime PGG is now being developed for the treatment of multiple cancers in combination with tumor-targeting Mabs.Initial clinical indications of focus have been 2nd-3rd line metastatic colorectal cancer (CRC) in combination with cetuximab (Erbitux?), which is currently in Phase 3 development;1st line non-small-cell lung cancer (NSCLC) in combination with cetuximab or bevacizumab (Avastin?), which is currently in Phase 2b development;and chronic lymphocytic leukemia (CLL) in combination with rituximab (Rituxan?) and alemtuzumab (Campath?), which is currently in Phase 1b/2 development.Results from completed clinical CRC studies have been promising, consistently demonstrating a good safety profile with an approximate doubling in overall response rate (ORR) and median time to progression (TTP) compared to expected results in controls.Interim results from ongoing studies in the other indications have also been encouraging.Overall,Imprime PGG is a novel anti-cancer immunotherapy that appears to have efficacy in multiple indications with multiple Mabs, supporting a broad-based opportunity for improving cancer treatment when used in conjunction with Mab therapy.Specific nonclinical and clinical data will be presented and discussed.
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