@article{632e5ad7bc1146de9d52272fdcb27950,
title = "Vaccine-induced intratumoral lymphoid aggregates correlate with survival following treatment with a neoadjuvant and adjuvant vaccine in patients with resectable pancreatic adenocarcinoma",
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.",
author = "Lei Zheng and Ding Ding and Edil, {Barish H.} and Carol Judkins and Durham, {Jennifer N.} and Thomas, {Dwayne L.} and Bever, {Katherine M.} and Guanglan Mo and Solt, {Sara E.} and Hoare, {Jessica A.} and Raka Bhattacharya and Qingfeng Zhu and Arsen Osipov and Beth Onner and Purtell, {Katrina A.} and Hongyan Cai and Rose Parkinson and Amy Hacker-Prietz and Herman, {Joseph M.} and Le, {Dung T.} and Azad, {Nilofer S.} and {de Jesus-Acosta}, {Ana M.C.} and Blair, {Alex B.} and Victoria Kim and Soares, {Kevin C.} and Lindsey Manos and Cameron, {John L.} and Makary, {Martin A.} and Weiss, {Matthew J.} and Schulick, {Richard David} and Jin He and Wolfgang, {Christopher L.} and Thompson, {Elizabeth D.} and Anders, {Robert A.} and Elizabeth Sugar and Jaffee, {Elizabeth M.} and Laheru, {Daniel A.}",
note = "Funding Information: This work was supported mainly by the Viragh Foundation and the Skip Viragh Pancreatic Cancer Center at Johns Hopkins (to D.A. Laheru, E.M. Jaffee), NIH grant R01 CA169702 (to L. Zheng), NIH grant K23 CA148964 (to L. Zheng), NIH grant R01 CA197296 (to L. Zheng, E.M. Jaffee), NIH SPORE grant P50 CA062924 (to E.M. Jaffee, D.A. Laheru, and L. Zheng), and NIH Cancer Center Support Grant P30 CA006973. Funding Information: L. Zheng reports grants from Merck, BMS, Halozyme, ITEOS, Novarock, Inxmed, AstraZeneca, and Amgen, as well as personal fees from Biosion, xilio, Novarock, Alphamab, Novagenesis, Mingruizhiyao, Datareve, QED, Johnson and Johnson, and Ambrx outside the submitted work; in addition, L. Zheng has a patent for Aduro with royalties paid. K.M. Bever reports grants from Merck and BMS outside the submitted work; Dr. Bever{\textquoteright}s spouse is employed by and owns stock in SOPHiA Genetics. J. Herman reports grants from 1440 Foundation; other from Pancreatic Cancer Action Network; and personal fees from Sirtex, BMS, and Medtronic outside the submitted work. D.T. Le reports grants from BMS, Merck, Aduro Biotech, Curegenix, Medivir, and Nouscom outside the submitted work. R.D. Schulick reports grants from NIH and Aduro Biotech during the conduct of the study. R.A. Anders reports personal fees from Merck and AstraZeneca; grants and personal fees from Bristol Myers Squibb, Rapt Therapuertics; and grants from Stand Up to Cancer during the conduct of the study. E.A. Sugar reports grants from Gateway for Cancer Research during the conduct of the study. E.M. Jaffee reports grants from Aduro Biotech, Bristol Myers Squibb, and NCI during the conduct of the study. Dr. Jaffee also reports personal fees from Genocea, DragonFly, Adaptive Biotech, CSTONE, and Achilles; grants from Lustgarten Foundation; and nonfinancial support from Parker Institute outside the submitted work. In addition, E.M. Jaffee has a patent for GVAX issued and licensed to Aduro Biotech. No disclosures were reported by the other authors. Publisher Copyright: {\textcopyright} 2020 American Association for Cancer Research.",
year = "2021",
month = mar,
day = "1",
doi = "10.1158/1078-0432.CCR-20-2974",
language = "English (US)",
volume = "27",
pages = "1278--1286",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "5",
}