Allogeneic vaccination for renal cell carcinoma: development and monitoring.
An allogeneic tumor cell vaccine should display a natural immunogenicity that allows the stimulation of tumor-reactive effector cells in patients. Furthermore, the vaccine should express antigens that are shared by many tumors to which patients are not tolerant. A variety of tumor peptides should be presented by different HLA-molecules due to limited MHC matching with recipients and last but not least, the vaccine should have a strong growth potential in vitro to allow adequate amounts of vaccine to be generated for long-term usage. In vitro and in situ studies with the renal cell carcinoma cell line RCC-26 demonstrate: (1) RCC-26 can induce complex allospecific responses through direct priming; (2) RCC-26 can not only reactivate cytotoxic T lymphocytes (CTL) of a memory phenotype but they also can induce de novo tumor-antigen associated responses in normal donors; (3) these cells present epitopes restricted by several MHC molecules, allowing the vaccination of patients matched for different HLA alleles; and (4) they stimulate HLA-A*0201-restricted T cells bearing characteristic T cell receptors (TCR). Thus, in addition to using limiting dilution killer and ELISPOT assays, molecular tracking of a tumor-specific TCR can be used to judge the development of antitumor reactivity and vaccine efficiency.
Department of Urology, Ludwig-Maximilians-University, Berlin, Germany.
H
H
Pohla
B
B
Frankenberger
B
B
Stadlbauer
R
R
Oberneder
A
A
Hofstetter
G
G
Willimsky
A
A
Pezzutto
B
B
Dörken
T
T
Blankenstein
D J
DJ
Schendel
D019496:Cancer Vaccines / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D066298:In Vitro Techniques; D007680:Kidney Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D008674:Metals, Rare Earth; D015166:Monitoring, Immunologic; D009368:Neoplasm Transplantation; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014184:Transplantation, Homologous; D014407:Tumor Cells, Cultured; D014611:Vaccination
D019496:Cancer Vaccines; D008674:Metals, Rare Earth; D011948:Receptors, Antigen, T-Cell