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Reduced Efficacy of Allogeneic versus Syngeneic Fibroblasts Modified to Secrete Cytokines as a Tumor Vaccine Adjuvant¹

Division of Surgical Oncology, University of Michigan, Ann Arbor, Michigan 48109

We examined the relative efficacy of allogeneic versus syngeneic fibroblasts admixed with tumor cells as a vaccine to induce antitumor T-cell reactivity. Allogeneic (3T3) or syngeneic (BLK) fibroblasts transfected to secrete equivalent amounts of GM-CSF were admixed with either D5 melanoma or MCA 207 sarcoma and inoculated s.c. into the flanks of C57BL/6 mice. Vaccine-primed lymph node (LN) cells were examined for in vivo antitumor reactivity in an adoptive transfer model. At fibroblast: tumor cell ratios of 1, allogeneic and syngeneic granulocyte macrophage colony-stimulating factor-secreting fibroblasts enhanced T-cell reactivity to tumor cells. However, at ratios of 2.4, the adjuvant effect induced by granulocyte macrophage colony-stimulating factor was not evident. Instead, we observed increased alloreactivity of primed LN cells against 3T3 targets as assessed by cytotoxicity and cytokine release assays, which was not observed with syngeneic fibroblasts. Moreover, with increasing numbers of allogeneic fibroblasts, there was a skewing of the T-cell Vß repertoire. These latter cells responded to tumor stimulation with the release of greater amounts of interleukin 10, which may account for the diminished antitumor reactivity observed in vivo. Allogeneic fibroblasts transduced to secrete interleukin 2 or IFN- also induced diminished tumor reactivity of primed LN cells. Syngeneic fibroblasts are superior to allogeneic fibroblasts as vehicles to deliver cytokines in tumor vaccines.

¹ This work was supported in part by NIH Grant PO1CA59327 and the Gillson Longenbaugh Foundation.

² Present address: Department of Gastroenterological Surgery, Tokyo Women's Medical College, Tokyo, Japan.

³ Present address: PCU. The National Cancer Center Hospital East, Tokyo, Japan.

⁴ To whom requests for reprints should be addressed, at University of Michigan Medical Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109. Phone: (313) 936-4392; Fax: (313) 936-5830; E-mail: aechang@umich.edu.

Received 1/10/97. Accepted 5/29/97.

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