PMID- 32925563 OWN - NLM STAT- MEDLINE DCOM- 20210902 LR - 20210902 IS - 1537-4513 (Electronic) IS - 1524-9557 (Linking) VI - 43 IP - 9 DP - 2020 Nov/Dec TI - 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. PG - 273-282 LID - 10.1097/CJI.0000000000000336 [doi] AB - 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 50x10 cells/administration) were injected intradermally q2wkx3 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. FAU - Faiena, Izak AU - Faiena I AD - Department of Urology, Institute of Urologic Oncology. FAU - Comin-Anduix, Begona AU - Comin-Anduix B AD - Department of Surgery, Division of Surgical-Oncology, Jonsson Comprehensive Cancer Center University of California Los Angeles and Parker Institute for Cancer Immunotherapy at UCLA. FAU - Berent-Maoz, Beata AU - Berent-Maoz B AD - Department of Medicine, Division of Hematology and Oncology. FAU - Bot, Adrian AU - Bot A AD - Kite Pharma Inc., A Gilead Company, Santa Monica, CA. FAU - Zomorodian, Nazy AU - Zomorodian N AD - Department of Urology, Institute of Urologic Oncology. FAU - Sachdeva, Ankush AU - Sachdeva A AD - Department of Urology, Institute of Urologic Oncology. FAU - Said, Jonathan AU - Said J AD - Department of Pathology, David Geffen School of Medicine at University of California. FAU - Cheung-Lau, Gardenia AU - Cheung-Lau G AD - Department of Surgery, Division of Surgical-Oncology, Jonsson Comprehensive Cancer Center University of California Los Angeles and Parker Institute for Cancer Immunotherapy at UCLA. FAU - Pang, Jia AU - Pang J AD - Department of Medicine, Division of Hematology and Oncology. FAU - Macabali, Mignonette AU - Macabali M AD - Department of Medicine, Division of Hematology and Oncology. FAU - Chodon, Thinle AU - Chodon T AD - Center for Immunotherapy, Roswell Park Cancer Institute, Buffalo, NY. FAU - Wang, Xiaoyan AU - Wang X AD - Department of General Internal Medicine and Healthy Services Research, University of California Los Angeles, Los Angeles. FAU - Cabrera, Paula AU - Cabrera P AD - Department of Medicine, Division of Hematology and Oncology. FAU - Kaplan-Lefko, Paula AU - Kaplan-Lefko P AD - Department of Medicine, Division of Hematology and Oncology. FAU - Chamie, Karim AU - Chamie K AD - Department of Urology, Institute of Urologic Oncology. FAU - Belldegrun, Arie S AU - Belldegrun AS AD - Department of Urology, Institute of Urologic Oncology. FAU - Pantuck, Allan J AU - Pantuck AJ AD - Department of Urology, Institute of Urologic Oncology. FAU - Drakaki, Alexandra AU - Drakaki A AD - Department of Urology, Institute of Urologic Oncology. AD - Department of Pathology, David Geffen School of Medicine at University of California. LA - eng SI - ClinicalTrials.gov/NCT01826877 GR - P30 CA016042/CA/NCI NIH HHS/United States GR - P30 AI028697/AI/NIAID NIH HHS/United States PT - Clinical Trial, Phase I PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - J Immunother JT - Journal of immunotherapy (Hagerstown, Md. : 1997) JID - 9706083 RN - 0 (Antigens, Neoplasm) RN - 0 (Cancer Vaccines) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) RN - EC 4.2.1.1 (CA9 protein, human) RN - EC 4.2.1.1 (Carbonic Anhydrase IX) SB - IM MH - Antigens, Neoplasm/*genetics/immunology MH - Cancer Vaccines/*administration & dosage/adverse effects/genetics/metabolism MH - Carbonic Anhydrase IX/*genetics/immunology MH - Carcinoma, Renal Cell/immunology/pathology/*therapy MH - Dendritic Cells/*immunology/metabolism MH - Disease Management MH - Granulocyte-Macrophage Colony-Stimulating Factor/*genetics/metabolism MH - Humans MH - Immunotherapy/adverse effects/methods MH - Kidney Neoplasms/immunology/pathology/*therapy MH - Treatment Outcome EDAT- 2020/09/15 06:00 MHDA- 2021/09/03 06:00 CRDT- 2020/09/14 15:44 PHST- 2020/09/15 06:00 [pubmed] PHST- 2021/09/03 06:00 [medline] PHST- 2020/09/14 15:44 [entrez] AID - 00002371-202011000-00002 [pii] AID - 10.1097/CJI.0000000000000336 [doi] PST - ppublish SO - J Immunother. 2020 Nov/Dec;43(9):273-282. doi: 10.1097/CJI.0000000000000336.