Ignite Creation Date:
2024-05-05 @ 6:38 PM
Last Modification Date:
2024-10-26 @ 9:35 AM
Study NCT ID:
NCT00515983
Status:
COMPLETED
Last Update Posted:
2007-08-14
First Post:
2007-08-10
Brief Title:
Vaccination of Melanoma Patients With Dendritic Cells Loaded With Allogeneic Apoptotic-Necrotic Melanoma Cells
Sponsor:
José Mordoh MD PhD
Organization:
José Mordoh MD PhD
Study Overview
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
Status:
COMPLETED
Status Verified Date:
2007-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 DCApo-Nec composed of autologous dendritic cells DCs loaded with a mixture of apoptoticnecrotic 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 DCApo-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 423 137 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 752 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 DCApo-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 p005 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 AMART-1 Ags were studied by tetramers binding in HLA-A0201 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 445 months post-surgery the stage IIC pt is NED 78 stage III pts are NED and 77 stage IV patients have progressed
Conclussions We conclude that DCApo-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
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 DCApo-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 423 137 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 752 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 DCApo-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 p005 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 AMART-1 Ags were studied by tetramers binding in HLA-A0201 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 445 months post-surgery the stage IIC pt is NED 78 stage III pts are NED and 77 stage IV patients have progressed
Conclussions We conclude that DCApo-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
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None