title: Gene therapy with autologous, interleukin 2-secreting tumor cells in patients with malignant melanoma.
abstract: We vaccinated metastatic melanoma patients with irradiated, autologous melanoma cells genetically engineered to secrete interleukin 2 (IL-2) to investigate whether an anti-tumor immune response would be induced. Melanoma cell cultures were established from surgical specimens and were engineered to secrete IL-2 by infection with recombinant retrovirus. Twelve patients were vaccinated subcutaneously one, two, or three times with approximately 10(7) irradiated, autologous, IL-2-secreting tumor cells. Treatment was well tolerated, with local reactions at 11 of 24 injection sites and minor systemic symptoms of fever and headache after 6 injections. One patient developed anti-tumor DTH after the first vaccination and showed an increased response after the second vaccination. Anti-autologous tumor CTLs could be detected prevaccination in the peripheral blood of seven patients and their activity increased after vaccination in four patients. No UICC-defined clinical responses were seen, but three patients had stable disease for 7-15 months, one of whom has not yet progressed (15+ months). Thus, patient vaccination with autologous, genetically engineered tumor cells is feasible and safe. Anti-tumor DTH and CTLs can be induced in some patients with such a vaccine.
authors.affiliation: CRC Centre for Cell and Molecular Biology, Chester Beatty Laboratories, London, UK.
authors.forename: K
authors.initials: K
authors.lastname: Palmer
authors.forename: J
authors.initials: J
authors.lastname: Moore
authors.forename: M
authors.initials: M
authors.lastname: Everard
authors.forename: J D
authors.initials: JD
authors.lastname: Harris
authors.forename: S
authors.initials: S
authors.lastname: Rodgers
authors.forename: R C
authors.initials: RC
authors.lastname: Rees
authors.forename: A K
authors.initials: AK
authors.lastname: Murray
authors.forename: R
authors.initials: R
authors.lastname: Mascari
authors.forename: J
authors.initials: J
authors.lastname: Kirkwood
authors.forename: P G
authors.initials: PG
authors.lastname: Riches
authors.forename: C
authors.initials: C
authors.lastname: Fisher
authors.forename: J M
authors.initials: JM
authors.lastname: Thomas
authors.forename: M
authors.initials: M
authors.lastname: Harries
authors.forename: S R
authors.initials: SR
authors.lastname: Johnston
authors.forename: M K
authors.initials: MK
authors.lastname: Collins
authors.forename: M E
authors.initials: ME
authors.lastname: Gore
mesh_terms: D000328:Adult; D019496:Cancer Vaccines / Q000276:immunology*; D017690:Cell Transplantation; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000628:therapy*; D008875:Middle Aged; D009368:Neoplasm Transplantation; D014182:Transplantation, Autologous; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D007376:Interleukin-2; D019444:Vaccines, DNA