title: Autologous tumor cell line-derived vaccine for patient-specific treatment of advanced renal cell carcinoma.
abstract: OBJECTIVE
  We previously reported the laboratory methodology for producing patient-specific irradiated autologous tumor-cell products derived from short-term cultured tumor cells from resected renal cell carcinoma, and described preliminary clinical results. In this study, we report the final clinical results and efforts to define vaccine potency on the basis of clinical outcome for these 25 patients with advanced renal cell carcinoma.
  
  
  METHODS
  Approximately 10(8) cells from successful short-term cell lines were irradiated, frozen in aliquots of 10(7) cells, then thawed and administered subcutaneously (s.c.) once a week for 3 weeks, then once a month for 5 months. Patients included 19 men and 6 women, who were 43-82 years of age. Six (6) patients had a large primary lesion, 2 patients had regionally advanced disease, 3 patients had been rendered disease-free by surgical resection of distant metastases, and 14 patients had measurable distant metastatic disease.
  
  
  RESULTS
  The vaccines were well tolerated, and no delayed autoimmune effects were documented. Delayed-type hypersensitivity (DTH) tests of irradiated tumor cells were positive in only 1 of 25 patients at week 0, but converted to positive in 6 of 18 patients of DTH-negative patients who were retested at week 4. Objective response rate in patients who had measurable metastatic disease was 0 of 14 patients. With a median follow-up of greater than 7 years from the date of the first DTH test, median survival is 33.4 months, 5-year survival is 43%, and 10 patients are alive 3-12 years later. The 7 DTH+ patients survived a median of 2.5 years, and 3 patients are alive after 3, 4, and 7 years. There was no correlation between the number of irradiated cells or viable irradiated cells injected and tumor DTH reactivity or survival.
  
  
  CONCLUSIONS
  This approach is feasible and the therapy is well tolerated, but clinical benefit was not established in this trial. Any further exploration of this product should be limited to the adjuvant setting in a randomized trial.
authors.affiliation: Hoag Cancer Center, Newport Beach, CA 92658, USA. rdillman@hoaghospital.org
authors.forename: Robert
authors.initials: R
authors.lastname: Dillman
authors.forename: Neil
authors.initials: N
authors.lastname: Barth
authors.forename: Louis
authors.initials: L
authors.lastname: Vandermolen
authors.forename: Khosrow
authors.initials: K
authors.lastname: Mahdavi
authors.forename: Linda
authors.initials: L
authors.lastname: Beutel
authors.forename: Cristina
authors.initials: C
authors.lastname: de Leon
authors.forename: Carol
authors.initials: C
authors.lastname: DePriest
authors.forename: Shankar
authors.initials: S
authors.lastname: Nayak
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines; D002292:Carcinoma, Renal Cell / Q000401:mortality / Q000628:therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed; D016233:Immunotherapy, Active / Q000379:methods*; D007680:Kidney Neoplasms / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D013997:Time Factors; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured / Q000378:metabolism
chemical_list: D019496:Cancer Vaccines