CLINICAL TRIAL article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicImmune landscape and therapeutic barriers in gastrointestinal cancersView all 7 articles
Safety and immunologic impact of neoadjuvant/adjuvant GVAX, cyclophosphamide, pembrolizumab, and anti-CSF1R agent IMC-CS4 in pancreatic adenocarcinoma
Provisionally accepted
Arielle UrmanYingjun DingJennifer Durham
Hao WangHanfei Qi
Amol NarangRichard Burkhart
Jin HeDung LeDaniel LaheruElizabeth JaffeeKatrina PurtellCharmaine Waisome-StephensMeizheng LiuLei Zheng
Ana De Jesus Acosta*- Johns Hopkins Hospital, Baltimore, United States
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
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. Trial Registration: Clinicaltrials.gov ID: NCT03153410
Keywords: Borderline resectable pancreaic cancer, CSF1R (Colony stimulating factor 1 receptor), Immunotherapy, neoadjuvant therapy (NAC), pancreas adenocarcinoma
Received: 29 Sep 2025; Accepted: 09 Feb 2026.
Copyright: © 2026 Urman, Ding, Durham, Wang, Qi, Narang, Burkhart, He, Le, Laheru, Jaffee, Purtell, Waisome-Stephens, Liu, Zheng and De Jesus Acosta. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ana De Jesus Acosta
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.