Immunogenetic therapy of human melanoma utilizing autologous tumor cells transduced to secrete granulocyte-macrophage colony-stimulating factor

We performed a clinical study of five patients with melanoma to evaluate th e immunobiological effects of retrovirally transduced autologous tumor cell s given as a vaccine to prime draining lymph nodes, Patients were inoculate d with both wild-type (WT) and GM-CSF gene-transduced tumor cells in differ ent extremities. Approximately 7 days later, vaccine-primed lymph nodes (VP LNs) were removed. There was an increased infiltration of dendritic cells ( DCs) in the GM-CSF-secreting vaccine sites compared with the WT vaccine sit es. This resulted in a greater number of cells harvested from the GM-CSF-VP LNs compared with the WT-VPLNs at a time when serum levels of GM-CSF were n ot detectable, Four of five patients proceeded to have the adoptive transfe r of GM-CSF-VPLN cells secondarily activated and expanded ex vivo with anti -CD3 MAb and IL-2, One patient had a durable complete remission of metastat ic tumor. Utilizing cytokine (IFN-gamma, GM-CSF, IL-10) release assays, GM- CSF-VPLN T cells manifested diverse responses when exposed to tumor antigen in vitro. In two of two patients, GM-CSF-VPLN T cell responses were differ ent from those of matched WT-VPLN cells, This study documents measurable im munobiologic differences of GM-CSF-transduced tumor cells given as a vaccin e compared with WT tumor cells, The complete tumor remission in one patient provides a rationale to pursue this approach further.