Use of murine models of cytokine-secreting tumor vaccines to study feasibility and toxicity issues critical to designing clinical trials

Elizabeth M. Jaffee, Audrey Lazenby, Janet Meurer, Fray Marshall, Karen M. Hauda, Christy Counts, Herbert Hurwitz, Jonathan W. Simons, Hyam I. Levitsky, Drew M. Pardoll

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

In preclinical models, tumor cells genetically altered to secrete cytokines or express costimulatory molecules can generate systemic antitumor immunity. In some studies, these tumor vaccines have been shown to eradicate micrometastases. These results have lead to the initiation of numerous Phase I clinical trials employing either genetically modified autologous or allogeneic tumor vaccines. We address a number of feasibility and toxicity issues critical to the design of these immunotherapy trials, using the B16 melanoma vaccine model. First, we demonstrated the efficacy of freeze/thawed vaccine cells, a process required for conducting clinical trials with large numbers of vaccine cells. Second, we performed pharmacokinetic studies and showed peak levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) that are far below levels expected to result in significant side effects in patients. Third, we performed autoimmune toxicity studies using the RENCA renal and B16 melanoma tumor vaccines and failed to demonstrate evidence of significant histologic or functional abnormalities. Overall, these novel studies address important issues that should be considered in the design of clinical trials evaluating genetically modified tumor vaccines.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalJournal of Immunotherapy
Volume18
Issue number1
DOIs
StatePublished - Jul 1995

    Fingerprint

Keywords

  • Cellular immunotherapy
  • Gene transfer
  • Tumor immunology
  • Tumor vaccines
  • Vaccine administration

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

Cite this

Jaffee, E. M., Lazenby, A., Meurer, J., Marshall, F., Hauda, K. M., Counts, C., Hurwitz, H., Simons, J. W., Levitsky, H. I., & Pardoll, D. M. (1995). Use of murine models of cytokine-secreting tumor vaccines to study feasibility and toxicity issues critical to designing clinical trials. Journal of Immunotherapy, 18(1), 1-9. https://doi.org/10.1097/00002371-199507000-00001