Hubbard, Joleen M.; Toke, Eniko R.; Moretto, Roberto; Graham, Rondell P.; Youssoufian, Hagop; Lorincz, Orsolya; Molnar, Levente; Csiszovszki, Zsolt; Mitchell, Jessica L.; Wessling, Jaclynn; Toth, Jozsef; Cremolini, Chiara published the artcile< Safety and activity of PolyPEPI1018 combined with maintenance therapy in metastatic colorectal cancer: an open-label, multicenter, phase Ib study>, Application In Synthesis of 1492-18-8, the main research area is PolyPEPI1018 tumor associated antigen metastatic colorectal cancer.
Although chemotherapy is standard of care for metastatic colorectal cancer (mCRC), immunotherapy has no role in microsatellite stable (MSS) mCRC, a “”cold”” tumor. PolyPEPI1018 is an off-the-shelf, multi-peptide vaccine derived from 7 tumor-associated antigens (TAA) frequently expressed in mCRC. This study assessed PoIyPEPI1018 combined with first-line maintenance therapy in patients with MSS mCRC. Patients and Methods: Eleven patients with MSS mCRC received PolyPEPI1018 and Montanide ISA51VG adjuvant s.c., combined with tluoropyrimidine/biol. following first-line induction with chemotherapy and a biol. (NCT03391232). In Part A of the study, 5 patients received a single dose; in Part B, 6 patients received up to three doses of Poly- PEPI1018 every 12 wk. The primary objective was safety; secondary objectives were preliminary efficacy, immunogenicity at peripheral and tumor level, and immune correlates. PolyPEPI1018 vaccination was safe and well tolerated. No vaccine-related serious adverse event occurred. Eighty percent of patients had CD8+ T-cell responses against ≥3 TAAs. Increased d. of tumor-infiltrating lymphocytes were detected post-treatment for 3 of 4 patients’ liver biopsies, combined with increased expression of immune-related gene signatures. Three patients had objective response according to REClSTv1.1, and 2 patients qualified for curative surgery. Longer median progression-free survival for patients receiving multiple doses compared with a single dose (12.5 vs. 4.6 mo; P = 0.017) suggested a dose-efficacy correlation. The host HLA genotype predicted multi-antigen specific T-cell responses (P = 0.01) indicative of clin. outcome. PolyPEPI1018 added to maintenance chemotherapy for patients with unresectable, MSS mCRC was safe and associated with specific immune responses and antitumor activity warranting further confirmation in a randomized, controlled setting.
Clinical Cancer Research published new progress about Adenocarcinoma. 1492-18-8 belongs to class alcohols-buliding-blocks, and the molecular formula is C20H21CaN7O7, Application In Synthesis of 1492-18-8.
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