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Published in: Cancer Immunology, Immunotherapy 2/2023

14-07-2022 | Vaccination | Original Article

Personalized tumor vaccine for pancreatic cancer

Authors: Shira Orr, Ling Huang, James Moser, Dina Stroopinsky, Omar Gandarilla, Cori DeCicco, Jessica Liegel, Cansu Tacettin, Adam Ephraim, Giulia Cheloni, Daniela Torres, Donald Kufe, Jacalyn Rosenblatt, Manuel Hidalgo, Senthil K. Muthuswamy, David Avigan

Published in: Cancer Immunology, Immunotherapy | Issue 2/2023

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Abstract

Background

Pancreatic cancer is a highly lethal malignancy often presenting with advanced disease and characterized by resistance to standard chemotherapy. Immune-based therapies such checkpoint inhibition have been largely ineffective such that pancreatic cancer is categorized as an immunologically “cold tumor”. In the present study, we examine the therapeutic efficacy of a personalized cancer vaccine in which tumor cells are fused with dendritic cells (DC) resulting in the broad induction of antitumor immunity.

Results

In the KPC spontaneous pancreatic cancer murine model, we demonstrated that vaccination with DC/KPC fusions led to expansion of pancreatic cancer specific lymphocytes with an activated phenotype. Remarkably, vaccination led to a reduction in tumor bulk and near doubling of median survival in this highly aggressive model. In a second murine pancreatic model (Panc02), vaccination with DC/tumor fusions similarly led to expansion of tumor antigen specific lymphocytes and their infiltration to the tumor site. Having shown efficacy in immunocompetent murine models, we subsequently demonstrated that DC/tumor fusions generated from primary human pancreatic cancer and autologous DCs potently stimulate tumor specific cytotoxic lymphocyte responses.

Conclusions

DC/tumor fusions induce the activation and expansion of tumor reactive lymphocytes with the capacity to infiltrate into the pancreatic cancer tumor bed.
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Metadata
Title
Personalized tumor vaccine for pancreatic cancer
Authors
Shira Orr
Ling Huang
James Moser
Dina Stroopinsky
Omar Gandarilla
Cori DeCicco
Jessica Liegel
Cansu Tacettin
Adam Ephraim
Giulia Cheloni
Daniela Torres
Donald Kufe
Jacalyn Rosenblatt
Manuel Hidalgo
Senthil K. Muthuswamy
David Avigan
Publication date
14-07-2022
Publisher
Springer Berlin Heidelberg
Published in
Cancer Immunology, Immunotherapy / Issue 2/2023
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-022-03237-x

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