Cancer vaccine development: Protein transfer of membrane-anchored cytokines and immunostimulatory molecules

Ashley M Cimino-Mathews, Purani Palaniswami, Andrew C. Kim, Periasamy Selvaraj

Research output: Contribution to journalArticle

Abstract

Many tumor cells escape host-immune recognition by the down-regulation or lack of immunostimulatory molecules. Expression of immunostimulatory molecules on tumor cells by gene transfer can be used to induce an antitumor immune response. However, we have previously shown that protein transfer of glycosyl-phosphatidylinositol (GPI)-linked costimulatory molecules is a successful alternative to traditional gene transfer in preparing such a tumor vaccine. Vaccination with membranes modified by protein transfer to express GPI-linked B7.1 (CD80), a costimulatory adhesion molecule, induces protective immunity in mice and allogeneic antitumor T-cell proliferation in humans in vitro. Our goal is to develop an optimal tumor vaccine using tumor membranes modified by protein transfer to target and stimulate antigen-presenting cells (APCs) and T cells. We have investigated the efficacy of expressing GPI-anchored cytokine molecules on the surface of tumor cells. Expression of interleukin-12 (IL-12) on tumor-cell membranes in a GPI-anchored form induces a strong antitumor immune response that is comparable to the effects of secretory IL-12. Because many cytokines act synergistically, we are testing the membrane expression and immunostimulatory effects of cytokines individually as well as in combination to determine potential complementary effects of coexpression on the antitumor immune response. Ultimately, the protein-transfer vaccination may be used in humans alone or in multimodal combination therapies to induce tumor regression and to serve as a protective measure to prevent postsurgical secondary metastases.

Original languageEnglish (US)
Pages (from-to)231-240
Number of pages10
JournalImmunologic Research
Volume29
Issue number1-3
DOIs
StatePublished - 2004
Externally publishedYes

Fingerprint

Cancer Vaccines
Glycosylphosphatidylinositols
Membrane Proteins
Cytokines
Neoplasms
Interleukin-12
Vaccination
Tumor Escape
T-Lymphocytes
Antigen-Presenting Cells
Genes
Immunity
Proteins
Down-Regulation
Cell Proliferation
Cell Membrane
Neoplasm Metastasis
Membranes

Keywords

  • CD80
  • Costimulation
  • Cytokines
  • GPI
  • IL-12
  • IL-2

ASJC Scopus subject areas

  • Immunology

Cite this

Cancer vaccine development : Protein transfer of membrane-anchored cytokines and immunostimulatory molecules. / Cimino-Mathews, Ashley M; Palaniswami, Purani; Kim, Andrew C.; Selvaraj, Periasamy.

In: Immunologic Research, Vol. 29, No. 1-3, 2004, p. 231-240.

Research output: Contribution to journalArticle

Cimino-Mathews, Ashley M ; Palaniswami, Purani ; Kim, Andrew C. ; Selvaraj, Periasamy. / Cancer vaccine development : Protein transfer of membrane-anchored cytokines and immunostimulatory molecules. In: Immunologic Research. 2004 ; Vol. 29, No. 1-3. pp. 231-240.
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