PHASE-I STUDY OF IMMUNOTHERAPY OF CUTANEOUS METASTASES OF HUMAN CARCINOMA USING ALLOGENEIC AND XENOGENEIC MHC DNA-LIPOSOME COMPLEXES

The generation of strong tumor-specific immunity by in situ gene thera py is an attractive approach for the eradication of human cancer lesio ns. The objectives of this study were to examine the toxicities of emp loying the human HLA-A2, HLA-B13 and the murine H-2K(k) genes to gener ate tumor regression in patients with different cancer types via DC-Ch ol/DOPE cationic liposomes. The study was composed of two phase I/II t rials involving a total of 19 late-stage cancer patients. The patients were given four weekly injections of a DNA-liposome mixture directly into a cutaneous nodule. These procedures resulted in no significant c linical side-effects. The HLA-A2 gene gave the highest level of expres sion in situ. Although all patients treated had progressive systemic d isease and eventually succumbed to their disease, strong local respons es were generated in the treated nodules. Of the eight patients whose cutaneous: nodules received HLA-AP DNA, two completely regressed while four tumor nodules gave a partial local response. AN but one of the p atients who received HLA-A2-liposome mixtures and had a subsequent loc al response were either cervical or ovarian carcinoma patients. This l ocal response, seen in a group of patients who had relapsed stage IV s ystemic metastatic disease and were refractory to all available therap ies, demonstrates the generation of a strong local immune response fol lowing our in situ gene therapy protocol. Further studies to investiga te the use of HLA-AP, DC-Chol/DOPE cationic liposomes for immunotherap y of cervical and ovarian cancers are warranted.