title: Clinical experience with autologous tumor cell lines for patient-specific vaccine therapy in metastatic melanoma.
abstract: Because of their patient specificity and proliferative capacity, tumor cell lines established from autologous metastatic melanoma tumor samples may be an excellent immunogen for patient-specific vaccine therapy. Between October 1990 and July 1996, the Hoag Cancer Center cell biology laboratory received 136 fresh metastatic melanoma samples from 122 different patients. Tumor cell lines were successfully established for 92 of 136 samples (68%), for 87 of 122 patients (71%). Successful cultures were expanded to 10(8) cells (total culture time about 8 weeks), confirmed to be sterile, irradiated, and stored frozen in aliquots of 10(7) cells. Vaccines were prepared from 72 lines, and 62 vaccines were used in 57 different patients. Subcutaneous vaccination took place on weeks 1, 2 and 3, and then monthly for a total of 6 months. A delayed tumor hypersensitivity skin test (DTH) was administered at week zero and week 4. Various adjuvants were co-administered including BCG, alpha- or gamma-interferon, and GM-CSF. Patients were monitored for failure-free survival (FFS) and overall survival (OS) from the date of the first vaccination. Follow-up data is available for 52 patients, 27 who had no evident disease (NED) at the time of vaccination and 25 who had metastatic disease at the time of treatment. There were two partial responses which persisted 11.9 and 39.8+ months among the 25 patients who had detectable metastatic disease whün treatment was initiated (8%, 1 to 26%, 95%-Ci). Twenty patients had negative skin tests at week 0 and week 4; six were positive both times, and 13 converted their DTH from negative to positive, for a conversion rate of 13 of 33 (39%). Patients who received interferon-gamma and/or GM-CSF as an adjuvant had a higher rate of DTH conversion compared to patients who received other adjuvants (13 of 20 v 2 of 13, P = 0.003). For patients who were NED, nine of 19 (47%) converted their DTH test compared to four of 14 (29%) patients with metastatic disease (p = 0.33). For patients whose DTH converted from negative to positive after 3 weeks of vaccination, median FFS and OS were superior compared to patients whose DTH remained negative (19.4 v 4.0 months FFS, p = 0.0052 and 39.6 v 18.3 months OS, p = 0.0602). The autologous cell line approach to active specific immunotherapy is feasible for patients who have resectable foci of metastatic disease. Administration of such patient-specific vaccines improves survival for those patients who are NED at the time of vaccination and convert their DTH skin test, compared to those whose DTH test remains negative.
authors.affiliation: Hoag Cancer Center, Newport Beach, CA 92658, USA. rdillman@hoaghospital.org
authors.forename: R O
authors.initials: RO
authors.lastname: Dillman
authors.forename: S K
authors.initials: SK
authors.lastname: Nayak
authors.forename: N M
authors.initials: NM
authors.lastname: Barth
authors.forename: C
authors.initials: C
authors.lastname: DeLeon
authors.forename: L S
authors.initials: LS
authors.lastname: Schwartzberg
authors.forename: L E
authors.initials: LE
authors.lastname: Spitler
authors.forename: C
authors.initials: C
authors.lastname: Church
authors.forename: A A
authors.initials: AA
authors.lastname: O'Connor
authors.forename: L D
authors.initials: LD
authors.lastname: Beutel
mesh_terms: D001500:BCG Vaccine / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000009:adverse effects; D018929:Cell Culture Techniques / Q000379:methods; D002460:Cell Line; D018572:Disease-Free Survival; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D006968:Hypersensitivity, Delayed; D007372:Interferons / Q000627:therapeutic use; D008545:Melanoma / Q000276:immunology / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D001500:BCG Vaccine; D019496:Cancer Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007372:Interferons