Phase 1 Trial of Allogeneic Gene-Modified Tumor Cell Vaccine RCC-26/CD80/IL-2 in Patients with Metastatic Renal Cell Carcinoma

Autor: Gerald Willimsky, Heike Pohla, Michael Siebels, Ronald Frank, Antonio Pezzutto, Dolores J. Schendel, Christian G. Stief, Ralph Oberneder, Bernhard Frankenberger, Alexander Buchner, Andrea Baur-Melnyk, Alfons Hofstetter, Joachim Kopp, Thomas Blankenstein
Rok vydání: 2010
Předmět:
Male
Oncology
Lung Neoplasms
T-Lymphocytes
Genetic enhancement
Lymphocyte Activation
Immunoenzyme Techniques
Renal cell carcinoma
Medicine
Hypersensitivity
Delayed
Oligonucleotide Array Sequence Analysis
Brain Neoplasms
Reverse Transcriptase Polymerase Chain Reaction
Vaccination
Middle Aged
Kidney Neoplasms
Recombinant Proteins
Response Evaluation Criteria in Solid Tumors
B7-1 Antigen
Molecular Medicine
Female
Adult
medicine.medical_specialty
Blotting
Western
Bone Neoplasms
Cancer Vaccines
Interferon-gamma
Immune system
Antigens
Neoplasm
Internal medicine
HLA-A2 Antigen
Biomarkers
Tumor
Genetics
Carcinoma
Humans
RNA
Messenger
Carcinoma
Renal Cell
Molecular Biology
Aged
HLA-A Antigens
business.industry
Gene Expression Profiling
Vaccine trial
medicine.disease
Minimal residual disease
Immunology
Feasibility Studies
Interleukin-2
business
Zdroj: Human Gene Therapy. 21:285-297
ISSN: 1557-7422
1043-0342
Popis: Preclinical studies showed that the allogeneic tumor cell line RCC-26 displayed natural immunogenic potential that was enhanced through expression of CD80 costimulatory molecules and secretion of interleukin-2. Here we report the study of RCC-26/CD80/IL-2 cells in a phase 1 vaccine trial of renal cell carcinoma patients with metastatic disease (mRCC). Fifteen patients of the HLA-A*0201 allotype, with at least one metastatic lesion, were included. Irradiated vaccine cells were applied in increasing doses of 2.5, 10, and 40 x 10(6) cells over 22 weeks. Primary study parameters included safety and toxicity. Sequential blood samples were analyzed by interferon-gamma enzyme-linked immunospot assays to detect tumor antigen-associated (TAA) effector cells. The vaccine was well tolerated and the designated vaccination course was completed in 9 of 15 patients. Neither vaccine-induced autoimmunity nor systemic side effects were observed. Delayed-type hypersensitivity skin reactions were detected in 11 of 12 evaluated patients and were particularly strong in patients with prolonged survival. In parallel, vaccine-induced immune responses against vaccine or overexpressed TAA were detected in 9 of 12 evaluated patients. No tumor regressions occurred according to RECIST (Response Evaluation Criteria in Solid Tumors) criteria; however, median time to progression was 5.3 months and median survival was 15.6 months, indicating substantial disease stabilization. We conclude that vaccine use was safe and feasible in mRCC. Clinical benefits were limited in these patients with advanced disease; however, immune monitoring revealed vaccine-induced responses against multiple TAAs in the majority of study participants. These results suggest that this vaccine could be useful in combination therapies and/or minimal residual disease.
Databáze: OpenAIRE
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