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Sponsored by: |
José Mordoh, M.D., Ph.D. |
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Information provided by: | José Mordoh, M.D., Ph.D. |
ClinicalTrials.gov Identifier: | NCT00515983 |
Background: Sixteen melanoma patients (1 stage IIC, 8 stage III, and 7 stage IV) were treated in a Phase I study to evaluate safety and immune responses, with a vaccine (DC/Apo-Nec) composed of autologous dendritic cells (DCs) loaded with a mixture of apoptotic/necrotic melanoma cell lines (Apo-Nec).
Methods: PBMC were obtained from leukapheresis and DCs were generated from monocytes cultured in the presence of GM-CSF and IL-4 in serum-free medium. Immature DCs (iDCs) were loaded with gamma-irradiated Apo-Nec cells and injected id without adjuvant. Cohorts of four patients were given four vaccines with 5, 10, 15, or 20 x106 DC/Apo-Nec per vaccine, two weeks apart.
Results: The vaccine was well tolerated in all patients. Toxicity to vaccine was mild, and the toxicity-limiting dose has not been reached. We found that 42.3 ±13.7 % melanoma patients´ iDCs were able to phagocyte Apo-Nec cells wich induced DCs maturation, as evidenced by increased expression of CD83, CD80, CD86, HLA class I and II compared to iDCs. Also, after phagocytosis, a 75.2 ±16 % reduction in Dextran-FITC endocytosis was observed compared to iDCs. CCR7 was upregulated upon Apo-Nec phagocytosis in DCs from all patients and accordingly in vitro DC/Apo-Nec cells were able to migrate towards MIP-3 beta. The DTH score increased significatively in the patients after the first vaccination and slightly decreased by the fourth vaccine (Mann-Whitney Test, p<0.05). For patient #1 a positive DTH reaction was detected to her own tumor irradiated cells. The presence of CD8+ T lymphocytes specific to gp100 and Melan A/MART-1 Ags were studied by tetramers binding in HLA-A*0201 patients (7 /15 patients) before and after vaccination. Two patients who remain NED increased Ags their specific T lymphocytes after vaccination. No humoral responses to Apo-Nec cells were detected. With a mean follow-up of 44.5 months post-surgery, the stage IIC pt is NED, 7/8 stage III pts are NED and 7/7 stage IV patients have progressed.
Conclussions: We conclude that DC/Apo-Nec vaccine is well tolerated, it induces specific immunity against melanoma Ags and in stage III patients it may prolong disease-free survival, affording protection from relapse in an adjuvant setting.
Condition | Intervention | Phase |
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Melanoma |
Biological: DC/Apo-Nec |
Phase I |
Study Type: | Interventional |
Study Design: | Treatment, Single Blind (Subject), Dose Comparison, Single Group Assignment, Safety/Efficacy Study |
Official Title: | Phase I Clinical Trial of a Therapeutic Vaccine Composed of Autologous Dendritic Cells Loaded With Allogeneic Apoptotic Tumor Cells in Patients With Melanoma Stages IIB, IIC, III and IV |
Enrollment: | 16 |
Study Start Date: | October 2004 |
Study Completion Date: | December 2005 |
Ages Eligible for Study: | 17 Years to 60 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Argentina, Capital Federal | |
Instituto Médico Alexander Fleming | |
Buenos Aires, Capital Federal, Argentina, 1426 |
Study Director: | José Mordoh, MD,PhD | Unaffiliated |
Study ID Numbers: | 4484/04 |
Study First Received: | August 10, 2007 |
Last Updated: | August 10, 2007 |
ClinicalTrials.gov Identifier: | NCT00515983 |
Health Authority: | Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica |
melanoma dendritic cells apoptotic/necrotic cells therapeutic vaccine |
Neuroectodermal Tumors Necrosis Nevus, Pigmented Neoplasms, Germ Cell and Embryonal |
Neuroepithelioma Nevus Neuroendocrine Tumors Melanoma |
Neoplasms Neoplasms by Histologic Type Neoplasms, Nerve Tissue Nevi and Melanomas |