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

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

Research output: Contribution to journalArticle

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
StatePublished - 1995

Fingerprint

Cancer Vaccines
Feasibility Studies
Clinical Trials
Cytokines
Experimental Melanomas
Vaccines
Neoplasm Micrometastasis
Clinical Trials, Phase I
Granulocyte-Macrophage Colony-Stimulating Factor
Immunotherapy
Immunity
Pharmacokinetics
Cell Count
Kidney
Neoplasms

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Immunology
  • Immunology and Allergy
  • Pharmacology

Cite this

Use of murine models of cytokine-secreting tumor vaccines to study feasibility and toxicity issues critical to designing clinical trials. / Jaffee, Elizabeth; Lazenby, Audrey; Meurer, Janet; Marshall, Fray; Hauda, Karen M.; Counts, Christy; Hurwitz, Herbert; Simons, Jonathan W.; Levitsky, Hyam I.; Pardoll, Andrew Mark.

In: Journal of Immunotherapy, Vol. 18, No. 1, 1995, p. 1-9.

Research output: Contribution to journalArticle

Jaffee, E, Lazenby, A, Meurer, J, Marshall, F, Hauda, KM, Counts, C, Hurwitz, H, Simons, JW, Levitsky, HI & Pardoll, AM 1995, 'Use of murine models of cytokine-secreting tumor vaccines to study feasibility and toxicity issues critical to designing clinical trials', Journal of Immunotherapy, vol. 18, no. 1, pp. 1-9.
Jaffee, Elizabeth ; Lazenby, Audrey ; Meurer, Janet ; Marshall, Fray ; Hauda, Karen M. ; Counts, Christy ; Hurwitz, Herbert ; Simons, Jonathan W. ; Levitsky, Hyam I. ; Pardoll, Andrew Mark. / Use of murine models of cytokine-secreting tumor vaccines to study feasibility and toxicity issues critical to designing clinical trials. In: Journal of Immunotherapy. 1995 ; Vol. 18, No. 1. pp. 1-9.
@article{390f164dbbeb4a07bec0fbe4742be180,
title = "Use of murine models of cytokine-secreting tumor vaccines to study feasibility and toxicity issues critical to designing clinical trials",
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.",
keywords = "Cellular immunotherapy, Gene transfer, Tumor immunology, Tumor vaccines, Vaccine administration",
author = "Elizabeth Jaffee and Audrey Lazenby and Janet Meurer and Fray Marshall and Hauda, {Karen M.} and Christy Counts and Herbert Hurwitz and Simons, {Jonathan W.} and Levitsky, {Hyam I.} and Pardoll, {Andrew Mark}",
year = "1995",
language = "English (US)",
volume = "18",
pages = "1--9",
journal = "Journal of Immunotherapy",
issn = "1524-9557",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Use of murine models of cytokine-secreting tumor vaccines to study feasibility and toxicity issues critical to designing clinical trials

AU - Jaffee, Elizabeth

AU - Lazenby, Audrey

AU - Meurer, Janet

AU - Marshall, Fray

AU - Hauda, Karen M.

AU - Counts, Christy

AU - Hurwitz, Herbert

AU - Simons, Jonathan W.

AU - Levitsky, Hyam I.

AU - Pardoll, Andrew Mark

PY - 1995

Y1 - 1995

N2 - 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.

AB - 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.

KW - Cellular immunotherapy

KW - Gene transfer

KW - Tumor immunology

KW - Tumor vaccines

KW - Vaccine administration

UR - http://www.scopus.com/inward/record.url?scp=0029129319&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029129319&partnerID=8YFLogxK

M3 - Article

C2 - 8535565

AN - SCOPUS:0029129319

VL - 18

SP - 1

EP - 9

JO - Journal of Immunotherapy

JF - Journal of Immunotherapy

SN - 1524-9557

IS - 1

ER -