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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



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



Cancer BioTherapy & Radiopharmaceuticals 17(1): 51-66



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 patient-specific immunotherapy. Patients and Methods: Surgically resected fresh tumor was obtained from patients with metastatic cancer. Successful tumor cell lines (5X107) were expanded to 108 cells, irradiated, and cryopreserved for clinical use. Following a baseline test of delayed-type hypersensitivity (DTH) to an i.d. injection of 106 irradiated autologous tumor cells, patients received 3 weekly s.c. injections of 107 cells, had a repeat DTH test at week-4, then received monthly vaccinations for 5 months. A positive DTH test was defined as gtoreq10 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). Conclusion: 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.

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Accession: 010885592

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PMID: 11915174

DOI: 10.1089/10849780252824073



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