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Zheng L, Ding D, Edil BH, et al. Vaccine-Induced Intratumoral Lymphoid Aggregates Correlate with Survival Following Treatment with a Neoadjuvant and Adjuvant Vaccine in Patients with Resectable Pancreatic Adenocarcinoma. Clin Cancer Res. 2020;27(5):1278-1286doi: 10.1158/1078-0432.CCR-20-2974.
Zheng, L., Ding, D., Edil, B. H., Judkins, C., Durham, J. N., Thomas, D. L., Bever, K. M., Mo, G., Solt, S. E., Hoare, J. A., Bhattacharya, R., Zhu, Q., Osipov, A., Onner, B., Purtell, K. A., Cai, H., Parkinson, R., Hacker-Prietz, A., Herman, J. M., Le, D. T., Azad, N. S., De Jesus-Acosta, A. M. C., Blair, A. B., Kim, V., Soares, K. C., Manos, L., Cameron, J. L., Makary, M. A., Weiss, M. J., Schulick, R. D., He, J., Wolfgang, C. L., Thompson, E. D., Anders, R. A., Sugar, E., Jaffee, E. M., & Laheru, D. A. (2021). Vaccine-Induced Intratumoral Lymphoid Aggregates Correlate with Survival Following Treatment with a Neoadjuvant and Adjuvant Vaccine in Patients with Resectable Pancreatic Adenocarcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research, 27(5), 1278-1286. https://doi.org/10.1158/1078-0432.CCR-20-2974
Zheng, Lei, et al. "Vaccine-Induced Intratumoral Lymphoid Aggregates Correlate with Survival Following Treatment with a Neoadjuvant and Adjuvant Vaccine in Patients with Resectable Pancreatic Adenocarcinoma." Clinical cancer research : an official journal of the American Association for Cancer Research vol. 27,5 (2021): 1278-1286. doi: https://doi.org/10.1158/1078-0432.CCR-20-2974
Zheng L, Ding D, Edil BH, Judkins C, Durham JN, Thomas DL, Bever KM, Mo G, Solt SE, Hoare JA, Bhattacharya R, Zhu Q, Osipov A, Onner B, Purtell KA, Cai H, Parkinson R, Hacker-Prietz A, Herman JM, Le DT, Azad NS, De Jesus-Acosta AMC, Blair AB, Kim V, Soares KC, Manos L, Cameron JL, Makary MA, Weiss MJ, Schulick RD, He J, Wolfgang CL, Thompson ED, Anders RA, Sugar E, Jaffee EM, Laheru DA. Vaccine-Induced Intratumoral Lymphoid Aggregates Correlate with Survival Following Treatment with a Neoadjuvant and Adjuvant Vaccine in Patients with Resectable Pancreatic Adenocarcinoma. Clin Cancer Res. 2021 Mar 01;27(5):1278-1286. doi: 10.1158/1078-0432.CCR-20-2974. Epub 2020 Dec 04. PMID: 33277370; PMCID: PMC7925374.
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Clin Cancer Res. 2021 Mar 01;27(5):1278-1286. doi: 10.1158/1078-0432.CCR-20-2974. Epub 2020 Dec 04.

Vaccine-Induced Intratumoral Lymphoid Aggregates Correlate with Survival Following Treatment with a Neoadjuvant and Adjuvant Vaccine in Patients with Resectable Pancreatic Adenocarcinoma.

Clinical cancer research : an official journal of the American Association for Cancer Research

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

Affiliations

  1. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. [email protected].
  2. Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  3. The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  4. The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  5. The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  6. The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  7. The Sol Goldman Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  8. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  9. Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  10. Department of Surgery and Cancer Center, University of Colorado School of Medicine, Aurora, Colorado.
  11. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  12. School of Public Health, Department of Biostatistics, Johns Hopkins University, Baltimore, Maryland.

PMID: 33277370 PMCID: PMC7925374 DOI: 10.1158/1078-0432.CCR-20-2974

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.

©2020 American Association for Cancer Research.

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