Clinical StudiesA 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 CarcinomaFaiena, Izak*; Comin-Anduix, Begoña†; Berent-Maoz, Beata‡; Bot, Adrian§; Zomorodian, Nazy*; Sachdeva, Ankush*; Said, Jonathan∥; Cheung-Lau, Gardenia†; Pang, Jia‡; Macabali, Mignonette‡; Chodon, Thinle¶; Wang, Xiaoyan#; Cabrera, Paula‡; Kaplan-Lefko, Paula‡; Chamie, Karim*; Belldegrun, Arie S.*; Pantuck, Allan J.*; Drakaki, Alexandra*,∥Author Information *Department of Urology, Institute of Urologic Oncology ‡Department of Medicine, Division of Hematology and Oncology ∥Department of Pathology, David Geffen School of Medicine at University of California †Department of Surgery, Division of Surgical-Oncology, Jonsson Comprehensive Cancer Center University of California Los Angeles and Parker Institute for Cancer Immunotherapy at UCLA #Department of General Internal Medicine and Healthy Services Research, University of California Los Angeles, Los Angeles §Kite Pharma Inc., A Gilead Company, Santa Monica, CA ¶Center for Immunotherapy, Roswell Park Cancer Institute, Buffalo, NY Trial registration: Clinicaltrials.gov, NCT01826877, registered April 4, 2013 (https://clinicaltrials.gov/ct2/show/NCT01826877). All patients gave written informed consent for participation. A.B., B.C.-A., A.J.P., A.D., A.S.B.: designed the study. I.F., A.S., N.Z., A.D., K.C.: treated patients and performed the clinical data acquisition. I.F., B.C.-A., J.S., A.D.: performed analysis of the clinical data. I.F., B.C.-A., B.B.-M., G.C.-L., J.P., M.M., P.C., P.K.-L., A.D.: analyzed and interpreted the immune assay. B.C.-A., T.C., B.B.-M., G.C.-L., J.P., M.M., P.C., P.K.L.: contributed to vaccine development. data. I.F., B.C.-A., A.D.: wrote the manuscript. Reprints: Izak Faiena, 300 Stein Plaza, Suite 331, Los Angeles, CA 90095 (e-mail: firstname.lastname@example.org). Journal of Immunotherapy: November/December 2020 - Volume 43 - Issue 9 - p 273-282 doi: 10.1097/CJI.0000000000000336 Buy SDC Metrics Abstract 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 50×106 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. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.