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Vaccine-Induced Intratumoral Lymphoid Aggregates Correlate with Survival Following Treatment with a Neoadjuvant and Adjuvant Vaccine in Patients with Resectable Pancreatic Adenocarcinoma
- Source :
- Clin Cancer Res
- Publication Year :
- 2021
- Publisher :
- American Association for Cancer Research (AACR), 2021.
-
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.
- Subjects :
- Male
0301 basic medicine
Oncology
Cancer Research
medicine.medical_specialty
Cyclophosphamide
medicine.medical_treatment
Cancer Vaccines
Article
03 medical and health sciences
0302 clinical medicine
Internal medicine
medicine
Clinical endpoint
Humans
Lymphocytes
Adjuvants, Vaccine
Antineoplastic Agents, Alkylating
Aged
business.industry
Immunotherapy
Middle Aged
Prognosis
medicine.disease
GVAX
Neoadjuvant Therapy
Vaccine therapy
Pancreatic Neoplasms
Survival Rate
Clinical trial
030104 developmental biology
030220 oncology & carcinogenesis
Feasibility Studies
Adenocarcinoma
Female
business
Adjuvant
Carcinoma, Pancreatic Ductal
Follow-Up Studies
medicine.drug
Subjects
Details
- ISSN :
- 15573265 and 10780432
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- Clinical Cancer Research
- Accession number :
- edsair.doi.dedup.....534abf5113ad35ad967526b033d79e86