REDUCED EFFICACY OF ALLOGENEIC VERSUS SYNGENEIC FIBROBLASTS MODIFIED TO SECRETE CYTOKINES AS A TUMOR VACCINE ADJUVANT

We examined the relative efficacy of allogeneic versus syngeneic fibro blasts admixed with tumor cells as a vaccine to induce antitumor T-cel l reactivity, Allogeneic (3T3) or syngeneic (BLK) fibroblasts transfec ted to secrete equivalent amounts of GM-CSF were admired with either D 5 melanoma or MCA 207 sarcoma and inoculated s.c. into the flanks of C 57BL/6 mice, Vaccine-primed lymph node (LN) cells were examined for in vivo antitumor reactivity in an adoptive transfer model, At fibroblas t: tumor cell ratios of less than or equal to 1, allogeneic and syngen eic granulocyte macrophage colony-stimulating factor-secreting fibrobl asts enhanced T-cell reactivity to tumor cells. However, at ratios of 2.4, the adjuvant effect induced by granulocyte macrophage colony-stim ulating factor was not evident. Instead, we observed increased allorea ctivity of primed LN cells against 3T3 targets as assessed by cytotoxi city and cytokine release assays, which was not observed with syngenei c fibroblasts, Moreover, with increasing numbers of allogeneic fibrobl asts, there was a skewing of the T-cell V beta repertoire, These latte r cells responded to tumor stimulation with the release of greater amo unts of interleukin 10, which may account for the diminished antitumor reactivity observed in vivo. Allogeneic fibroblasts transduced to sec rete interleukin 2 or IFN-gamma also induced diminished tumor reactivi ty of primed LN cells, Syngeneic fibroblasts are superior to allogenei c fibroblasts as vehicles to deliver cytokines in tumor vaccines.