RESUMO
The purpose of this study was to determine the safety of treating melanoma patients with retroviral vector-mediated interferon (IFN)-gamma gene-transduced autologous tumor cells. We designed a phase I study, in which irradiated, autologous, transduced melanoma cells expressing the IFN-gamma gene were injected subcutaneously every 2 weeks with escalating cell doses for six injections. Tumor tissue was harvested from 58 patients with metastatic melanoma. Twelve patients had sufficient expansion of autologous tumor (0.56-160 x 10(7) cells) and adequate IFN-gamma expression after gene transduction (2-79,000 U/10(6) cells/24 hours) for injections. Five patients received injections. No toxicity was attributed to the IFN-gamma retroviral vector in the patients injected. One of the injected patients remains disease-free after 13 injections, following the surgical removal of brain, adrenal, and lung metastases. We found that injections of autologous tumor cells transduced by IFN-gamma gene were well tolerated. However, the ability to develop primary autologous melanoma cell lines was limited, and only a minority of patients were injected.
Assuntos
Terapia Genética/métodos , Interferon gama/genética , Interferon gama/uso terapêutico , Melanoma/secundário , Melanoma/terapia , Adolescente , Adulto , Idoso , Anticorpos Antineoplásicos/sangue , Feminino , Técnicas de Transferência de Genes , Terapia Genética/efeitos adversos , Humanos , Injeções , Interleucina-2/uso terapêutico , Masculino , Melanoma/imunologia , Melanoma/mortalidade , Pessoa de Meia-Idade , Transplante de Neoplasias , Retroviridae/genética , Taxa de Sobrevida , Resultado do Tratamento , Células Tumorais Cultivadas/efeitos da radiação , Células Tumorais Cultivadas/virologiaRESUMO
A cell line used in the production of biologicals should be free of infectious agents, and 'described with respect to cytogenetic characteristics and tumorigenicity'. Vero, a continuous cell line derived from a normal African green monkey kidney, was examined for the presence of retroviruses and for tumorigenic potential. We were unable to detect the presence of retroviruses by reverse transcriptase assay, electron microscopy or hybridization of cellular genomic DNA with Mason-Pfizer monkey virus DNA probes. In addition, passage 156 Vero cells did not form progressively growing tumors in nude mice or grow with high efficiency in soft agarose.
