Safety and immunologic impact of neoadjuvant/adjuvant GVAX, cyclophosphamide, pembrolizumab, and anti-CSF1R agent IMC-CS4 in pancreatic adenocarcinoma

作者：Arielle Urman, Yingjun Ding, Jennifer N. Durham, Hao Wang, H. Qi, Amol Narang, Richard Burkhart, Jin He, Dung Le, Daniel Laheru, Elizabeth Thompson, Elizabeth Jaffee, Katrina Purtell, Charmaine Waisome-Stephens, Meizheng Liu, Lei Zheng, Ana M. De Jesus-Acosta · 发表于：Frontiers in Immunology · 年份：2026 · DOI：10.3389/fimmu.2026.1715761 · 被引用次数：1 · 研究领域：Pancreatic and Hepatic Oncology Research、Immune cells in cancer、Immunotherapy and Immune Responses

Background: We previously reported that an increased M1/M2 ratio and decreased PDL1+ M2- like tumor-associated macrophages (TAM) are associated with longer survival in patients with pancreatic adenocarcinoma (PDA). Targeting M2-like macrophages may improve patients' outcomes. In this pilot study, we hypothesized targeting M2-like macrophages, regulated by the colony stimulating factor-1 (CSF1) pathway, would be safe and induce an intratumoral immune response in patients with PDA. Methods: We tested perioperative combination immunotherapy (CI) with GM-CSF-secreting allogenic pancreatic tumor cell vaccine (GVAX)/cyclophosphamide (CY), pembrolizumab (Pem), and CSF1 receptor blockade (IMC-CS4) in patients with PDA. Patients received two neoadjuvant cycles of CI followed by surgery and four adjuvant cycles of CI. Subsequently, they received a booster Pem every 3 weeks and GVAX/CY every 6 months, for up to one year. The co-primary endpoints were safety and immune response in paired biopsies. Results: Nine patients were enrolled and treated in this study. We observed two immune related grade 3/4 AEs (diarrhea and rash). Comparison of paired biopsies showed five of eight evaluable patients met the immunologic endpoint with >80% increase in CD8+ T cells. The increase was at least 1.8 times the baseline median absolute deviation. Conclusion: CI has a manageable safety profile and leads to increased intratumoral cytotoxic effector T cells. Clinical Trial Registration: https://clinicaltr...