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
| Autor: | Beata Berent-Maoz, Ankush Sachdeva, Thinle Chodon, Paula Cabrera, Jonathan W. Said, Allan J. Pantuck, Gardenia Cheung-Lau, Alexandra Drakaki, Izak Faiena, Begoña Comin-Anduix, Paula Kaplan-Lefko, Arie S. Belldegrun, Xiaoyan Wang, Nazy Zomorodian, Karim Chamie, Jia Pang, Adrian Bot, Mignonette H. Macabali |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Oncology Cancer Research medicine.medical_specialty Immunology Cancer Vaccines Viral vector 03 medical and health sciences 0302 clinical medicine Immune system Antigens Neoplasm Renal cell carcinoma Internal medicine medicine Humans Immunology and Allergy Carbonic Anhydrase IX Adverse effect Carcinoma Renal Cell Pharmacology Leukopenia business.industry Disease Management Granulocyte-Macrophage Colony-Stimulating Factor Dendritic Cells medicine.disease Kidney Neoplasms Clear cell renal cell carcinoma Treatment Outcome 030104 developmental biology 030220 oncology & carcinogenesis Cohort Immunotherapy medicine.symptom business Progressive disease |
| Zdroj: | Journal of Immunotherapy. 43:273-282 |
| ISSN: | 1524-9557 |
| DOI: | 10.1097/cji.0000000000000336 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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