Vaccine-Induced Intratumoral Lymphoid Aggregates Correlate with Survival Following Treatment with a Neoadjuvant and Adjuvant Vaccine in Patients with Resectable Pancreatic Adenocarcinoma
Year: 2020
Type: article
Study design: Clinical Trial
Abstract: PURPOSE: Immunotherapy is currently ineffective for nearly all pancreatic ductal adenocarcinomas (PDAC), largely due to its tumor microenvironment (TME) that lacks antigen-experienced T effector cells (Teff). Vaccine-based immunotherapies are known to activate antigen-specific Teffs in the peripheral blood. To evaluate the effect of vaccine therapy on the PDAC TME, we designed a neoadjuvant and adjuvant clinical trial of an irradiated, GM-CSF-secreting, allogeneic PDAC vaccine (GVAX). PATIENTS AND METHODS: Eighty-seven eligible patients with resectable PDAC were randomly assigned (1:1:1) to receive GVAX alone or in combination with two forms of low-dose cyclophosphamide. Resected tumors following neoadjuvant immunotherapy were assessed for the formation of tertiary lymphoid aggregates (TLA) in response to treatment. The clinical endpoints are disease-free survival (DFS) and overall survival (OS). RESULTS: The neoadjuvant treatment with GVAX either alone or with two forms of low-dose cyclophosphamide is safe and feasible without adversely increasing the surgical complication rate. Patients in Arm A who received neoadjuvant and adjuvant GVAX alone had a trend toward longer median OS (35.0 months) than that (24.8 months) in the historical controls who received adjuvant GVAX alone. However, Arm C, who received low-dose oral cyclophosphamide in addition to GVAX, had a significantly shorter DFS than Arm A. When comparing patients with OS > 24 months to those with OS < 15 months, longer OS was found to be associated with higher density of intratumoral TLA. CONCLUSIONS: It is safe and feasible to use a neoadjuvant immunotherapy approach for PDACs to evaluate early biologic responses. In-depth analysis of TLAs is warranted in future neoadjuvant immunotherapy clinical trials.
Source: Clinical Cancer Research
Authors: Lei Zheng, Ding Ding, Barish H. Edil, Carol Judkins, Jennifer N. Durham, Dwayne L. Thomas, Katherine M. Bever, Guanglan Mo, Sara E. Solt, Jessica A. Hoare, Raka Bhattacharya, Qingfeng Zhu, Arsen Osipov, Beth Onner, Katrina A. Purtell, Hongyan Cai, Rose Parkinson, Amy Hacker-Prietz, Joseph M. Herman, Dung T. Le, Nilofer S. Azad, Ana M.C. De Jesus-Acosta, Alex B. Blair, Victoria Kim, Kevin C. Soares, Lindsey Manos, John L. Cameron, Martin A. Makary, Matthew J. Weiss, Richard D. Schulick, Jin He, Christopher L. Wolfgang, Elizabeth D. Thompson, Robert A. Anders, Elizabeth Sugar, Elizabeth M. Jaffee, Daniel A. Laheru
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: G1165598027, G1324540468, G160870376, G1733189847, G465951118, Interrogate the interaction between tumor cells and nerves in the tumor microenvironment of pancreatic cancer, Dissecting the mechanisms of immune tolerance within the pancreatic tumor's micro, G9000041231, G9000066787, G9000083017, G9000118357, G9000122394, G9000156078, Targeting the Stroma for Pancreatic Cancer Treatment, G952332958
OpenAlex ID: W3109229232