title: Irradiated cells from autologous tumor cell lines as patient-specific vaccine therapy in 125 patients with metastatic cancer: induction of delayed-type hypersensitivity to autologous tumor is associated with improved survival.
abstract: OBJECTIVE
  We established short-term cultures of pure tumor cells for use as autologous tumor cell vaccines in an effort to study the effects of patients-specific immunotherapy.
  
  
  METHODS
  Surgically resected fresh tumor was obtained from patients with metastatic cancer. Successful tumor cell lines (5 x 10(7)) were expanded to 10(8) cells, irradiated, and cryopreserved for clinical use. Following a baseline test of delayed-type hypersensitivity (DTH) to an i.d. injection of 10(6) irradiated autologous tumor cells, patients received 3 weekly s.c. injections of 10(7) cells, had a repeat DTH test at week-4, then received monthly vaccinations for 5 months. A positive DTH test was defined as > or = 10 mm induration; survival was determined from the first DTH test.
  
  
  RESULTS
  Short-term cell lines were successfully established for 299/695 patients (43%). Vaccines were prepared for 231 patients, 142 of whom were treated, and 125 had a baseline DTH test recorded. Median follow up at the time of analysis was greater than 5 years. There was no difference in survival for any of the following: gender, age > 50 years, melanoma histology, anergy to common recall antigens or baseline DTH test result. Only 17 patients had a positive DTH at baseline (14%), but DTH converted from negative to positive in 31/80 (39%) of those who were tested, and in 31/108 (29%) of all patients (intent-to-convert analysis). For the 48 patients who were DTH-positive at entry, or converted to DTH-positive, the median survival was 30.5 months and 5-year survival 41% compared to 11.4 months and 9% 5-year survival for 77 patients whose DTH was never positive (P2 = 0.003). However, survival was even better for patients whose DTH test converted to positive compared to patients who were DTH-positive at baseline (median 37.5 vs 11.9 mos, P2 = 0.066).
  
  
  CONCLUSIONS
  This patient-specific, cell culture-derived, autologous tumor cell vaccine induced anti-tumor immune reactivity that was associated with improved survival in patients with advanced cancer.
authors.affiliation: Hoag Cancer Center, One Hoag Drive, Building 41, Newport Beach, CA 92658, USA. rdillman@hoaghospital.org
authors.forename: Robert O
authors.initials: RO
authors.lastname: Dillman
authors.forename: Linda D
authors.initials: LD
authors.lastname: Beutel
authors.forename: Neil M
authors.initials: NM
authors.lastname: Barth
authors.forename: Cristina
authors.initials: C
authors.lastname: de Leon
authors.forename: Audrey A
authors.initials: AA
authors.lastname: O'Connor
authors.forename: Carol
authors.initials: C
authors.lastname: DePriest
authors.forename: Shankar K
authors.initials: SK
authors.lastname: Nayak
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology* / Q000401:mortality / Q000628:therapy; D012882:Skin Tests; D015996:Survival Rate; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured / Q000276:immunology* / Q000528:radiation effects
chemical_list: D019496:Cancer Vaccines