A Phase I, Open-label, Dose-escalation, and Cohort Expansion Study to Evaluate the Safety and Immune Response to Autologous Dendritic Cells Transduced With AdGMCA9 (DC-AdGMCAIX) in Patients With Metastatic Renal Cell Carcinoma.
Antigens, Neoplasm
/ genetics
Cancer Vaccines
/ administration & dosage
Carbonic Anhydrase IX
/ genetics
Carcinoma, Renal Cell
/ immunology
Dendritic Cells
/ immunology
Disease Management
Granulocyte-Macrophage Colony-Stimulating Factor
/ genetics
Humans
Immunotherapy
/ adverse effects
Kidney Neoplasms
/ immunology
Treatment Outcome
Journal
Journal of immunotherapy (Hagerstown, Md. : 1997)
ISSN: 1537-4513
Titre abrégé: J Immunother
Pays: United States
ID NLM: 9706083
Informations de publication
Date de publication:
Historique:
pubmed:
15
9
2020
medline:
3
9
2021
entrez:
14
9
2020
Statut:
ppublish
Résumé
Expression of carbonic-anhydrase IX (CAIX) in clear cell renal cell carcinoma (RCC) makes it an attractive vaccine target. We developed a fusion-gene construct, granulocyte-macrophage (GM) colony-stimulating factor+CAIX, delivered by an adenoviral vector (Ad) into autologous dendritic cells (DCs) in this phase 1 study. The injected immature DCs were expected to stimulate an antigen-specific immune response against CAIX expressing RCC. Three dose-escalation cohorts (5, 15, and 50×10 cells/administration) were injected intradermally q2wk×3 doses based on a 3+3 design. The primary objective was the safety of the injections. Secondary objectives were immune responses using enzyme-linked immunosorbent spot, a serum biomarker panel, and clinical response. Fifteen patients with metastatic RCC were enrolled, and 9 patients received all 3 doses. No serious adverse events were seen. There were 3 (33%) patients with grade 1 fatigue, 1 of whom subsequently experienced grade 2 fatigue. One patient (11%) experienced grade 1-2 leukopenia. Only 1 patient (11%) experienced grade 2 flu-like symptoms. Of the 9 patients who received treatment, 1 expired of progressive disease, 2 patients were lost to follow-up and 6 patients are alive. Of the 6 patients, 5 have progressive disease, and 1 has completed treatment with stable disease at 27 months follow-up. Immune response measurements appeared more robust in higher dose cohorts, which appeared to be related to patients with stable disease at 3 months. These early data show that autologous immature DC-AdGMCAIX can be safely given to metastatic RCC patients without any serious adverse events with CAIX-specific immune response elicited by the treatment. These preliminary data support further study of Ad-GMCAIX, particularly with combination therapies that may enhance clinical activity.
Identifiants
pubmed: 32925563
doi: 10.1097/CJI.0000000000000336
pii: 00002371-202011000-00002
doi:
Substances chimiques
Antigens, Neoplasm
0
Cancer Vaccines
0
Granulocyte-Macrophage Colony-Stimulating Factor
83869-56-1
CA9 protein, human
EC 4.2.1.1
Carbonic Anhydrase IX
EC 4.2.1.1
Banques de données
ClinicalTrials.gov
['NCT01826877']
Types de publication
Clinical Trial, Phase I
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
273-282Subventions
Organisme : NCI NIH HHS
ID : P30 CA016042
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI028697
Pays : United States
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