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Personalized tumor vaccine for pancreatic cancer

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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

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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Authors and Affiliations

  1. Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA, 02215, USA

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

  2. Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, USA

    Donald Kufe

Authors
  1. Shira Orr
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  2. Ling Huang
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  3. James Moser
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  4. Dina Stroopinsky
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  5. Omar Gandarilla
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  6. Cori DeCicco
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  7. Jessica Liegel
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  8. Cansu Tacettin
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  9. Adam Ephraim
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  10. Giulia Cheloni
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  11. Daniela Torres
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  12. Donald Kufe
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  13. Jacalyn Rosenblatt
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  14. Manuel Hidalgo
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  15. Senthil K. Muthuswamy
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  16. David Avigan
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Contributions

S.O contributed by writing the manuscript, designing and conducting experiments, and acquiring and analyzing data. L.H. and O.G. provided cells and helped writing the manuscript. J.M. and C.D. provided patient samples. D.S. helped in designing experiments, analyzing data, and writing of the manuscript. A.E. helped in conducting experiments. J.R. helped in designing experiments and analyzing the data. D.A. contributed to designing experiments, analyzing data and writing of the manuscript. J.L. and G.C. helped in experiment designing and data analysis while D.T. and C.T. helped in conducting experiments. DK, MH, and SM participated in experimental design and review of the manuscript.

Corresponding author

Correspondence to David Avigan.

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Competing interests

Funded in part by V Foundation.

Study approval

All animal studies were approved by BIDMC IACUC.

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Orr, S., Huang, L., Moser, J. et al. Personalized tumor vaccine for pancreatic cancer. Cancer Immunol Immunother 72, 301–313 (2023). https://doi.org/10.1007/s00262-022-03237-x

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  • DOI: https://doi.org/10.1007/s00262-022-03237-x

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