LOCOREGIONAL RESPONSE AND INCREASED NATURAL-KILLER ACTIVITY AFTER INTRATUMORAL INJECTION OF HLA-B7 BETA(2)-MICROGLOBULIN GENE IN PATIENTS WITH CANCER/

The purpose of this study was to assess the therapeutic potential of i njecting the gene for HLA-B7/beta(2)-microglobulin into the subcutaneo us metastatic nodules of patients who are refractory to conventional t reatments. The nine patients evaluated were divided into three groups and given escalating doses of DNA (20, 40, and 100 mu g of the HLA-B7 plasmid DNA/lipid complex for each group) every 2 weeks. Biopsy specim ens from the treated tumor nodules of all nine patients were positive For the presence of DNA and for HLA-B7 mRNA expression. Moreover, in s ix of the nine patients, immunohistology of tumor biopsy samples revea led the expression of recombinant HLA-B7 protein. Also, all nine patie nts showed an increase in NK activity in their circulating peripheral blood lymphocytes. In two lung cancer patients, one partial and one mi xed response was observed after gene transfer. These responses were co nfined to the treated nodules and the untreated locoregional lymph nod es; the lung masses showed no regression. Remission durations were 14 and 6 Reeks, respectively, and in a total of 35 cycles no significant toxicities were observed. Immunohistologic analysis revealed an increa sed infiltration of CD4(+) T cells, macrophages, and NK cells after th erapy. In two responding cases, direct intratumoral injection of an al logeneic class I gene could elicit an antitumor response in locoregion al areas, possibly through the activation of NK cells.