title: Phase I trial of retroviral vector-mediated interferon (IFN)-gamma gene transfer into autologous tumor cells in patients with metastatic melanoma.
abstract: 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.
authors.affiliation: Physician Reliance Network, Inc., and Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas 75246, USA.
authors.forename: J
authors.initials: J
authors.lastname: Nemunaitis
authors.forename: C
authors.initials: C
authors.lastname: Bohart
authors.forename: T
authors.initials: T
authors.lastname: Fong
authors.forename: W
authors.initials: W
authors.lastname: Meyer
authors.forename: G
authors.initials: G
authors.lastname: Edelman
authors.forename: R S
authors.initials: RS
authors.lastname: Paulson
authors.forename: D
authors.initials: D
authors.lastname: Orr
authors.forename: V
authors.initials: V
authors.lastname: Jain
authors.forename: J
authors.initials: J
authors.lastname: O'Brien
authors.forename: J
authors.initials: J
authors.lastname: Kuhn
authors.forename: K J
authors.initials: KJ
authors.lastname: Kowal
authors.forename: S
authors.initials: S
authors.lastname: Burkeholder
authors.forename: J
authors.initials: J
authors.lastname: Bruce
authors.forename: N
authors.initials: N
authors.lastname: Ognoskie
authors.forename: D
authors.initials: D
authors.lastname: Wynne
authors.forename: D
authors.initials: D
authors.lastname: Martineau
authors.forename: D
authors.initials: D
authors.lastname: Ando
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000912:Antibodies, Neoplasm / Q000097:blood; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007267:Injections; D007371:Interferon-gamma / Q000235:genetics* / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000627:therapeutic use; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000401:mortality / Q000556:secondary* / Q000628:therapy*; D008875:Middle Aged; D009368:Neoplasm Transplantation; D012190:Retroviridae / Q000235:genetics; D015996:Survival Rate; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured / Q000528:radiation effects / Q000821:virology
chemical_list: D000912:Antibodies, Neoplasm; D007376:Interleukin-2; D007371:Interferon-gamma