Cytokines as an adjuvant to tumor vaccines: Efficacy of local methods of delivery |
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Authors: | Shuji Kurane MD Marjorie T. Arca MD Atsushi Aruga MD PhD Robert A. Krinock BS John C. Krauss MD Dr. Alfred E. Chang MD |
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Affiliation: | (1) From the Division of Surgical Oncology, University of Michigan, Ann Arbor, Michigan, USA;(2) The Cleveland Clinic Foundation, Cleveland, Ohio, USA;(3) University of Michigan Medical Center, 1500 E. Medical Center Dr., 48109 Ann Arbor, MI, USA |
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Abstract: | Background: We examined alternative methods of delivering cytokines as an adjunct for priming lymph node (LN) cells draining sites of vaccine inoculation for the purpose of generating immune cells for adoptive immunotherapy.Methods: Using syngeneic murine tumors we examined the ability of IL-2, IL-4, or GM-CSF delivered locally to a site of tumor inoculum to induce antitumor reactive draining LN cells. Mice were inoculated subcutaneously with tumor cells transduced to secrete cytokine; tumor cells admixed with fibroblasts transduced to secrete cytokine; or intralesional inoculation of cytokine in established tumor to induce sensitized LN cells capable of mediating tumor regression in adoptive transfer.Results: Both IL-4 and GM-CSF cytokines were effective in enhancing the antitumor reactivity of vaccine-primed LN cells compared to IL-2, which was ineffective. The local delivery of GM-CSF by autocrine or paracrine secretion of genetically engineered cells, as well as direct intratumoral delivery was capable of upregulating LN sensitization compared to systemic administration, which did not.Conclusions: The local delivery of GM-CSF as an adjuvant for tumor vaccination can be accomplished by various methods, including direct injection, which avoids the need for gene transfer. |
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Keywords: | Vaccines IL-4-GM-CSF Gene therapy Adoptive immunotherapy |
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