THERAPEUTIC EFFICACY OF T-CELLS DERIVED FROM LYMPH-NODES DRAINING A POORLY IMMUNOGENIC TUMOR TRANSDUCED TO SECRETE GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR

We examined the host immune response to the poorly immunogenic B16-BL6 melanoma, which was transduced to secrete granulocyte-macrophage colo ny-stimulating factor (CM-CSF) (450 ng/10(6)/24 h). Tumor growth after subcutaneous inoculation was not significantly altered, although an i nflux of neutrophils and monocytes/macrophages was evident within tumo rs and draining lymph nodes (LNs). Immunization with irradiated transd uced cells did not induce systemic immunity to the parental tumor. How ever, vaccination with transduced tumors significantly augmented in vi vo sensitization of draining LN cells. These tumor-draining LN (TDLN) cells, when secondarily stimulated in vitro with anti-CD3 monoclonal a ntibodies and expanded in interleukin-2 (10 U/mL), exhibited greater r elease of GM-CSF and interferon-gamma against tumor compared with TDLN cells from animals with parental tumor. In adoptive immunotherapy, ac tivated LN cells draining transduced tumors mediated significant reduc tions of the numbers of established pulmonary metastases compared with LN cells draining parental tumor, which were ineffective. In addition , the therapeutic efficacy of LN cells draining transduced tumors was significantly better than LN cells primed in vivo with tumor cells adm ired with Corynebacterium parvum, which we have previously described a s an approach to generate immune cells. Thus, GM-CSF appears to be an important adjuvant in the induction of tumor immunity.