Cell-based vaccines for renal cell carcinoma: genetically-engineered tumor cells and monocyte-derived dendritic cells.
Initial vaccine developments for renal cell carcinoma (RCC) have concentrated on cell-based approaches in which tumor cells themselves provide mixtures of unknown tumor-associated antigens as immunizing agents. Antigens derived from autologous tumors can direct responses to molecular composites characteristic of individual tumors, whereas antigens derived from allogeneic tumor cells must be commonly shared by RCC. Three types of cell-based vaccine for RCC have been investigated: isolated tumor cell suspensions, gene modified tumor cells and dendritic cells (DCs) expressing RCC-associated antigens. Approaches using genetic modification of autologous RCC have included ex vivo modification of tumor cells or modification of tumors in vivo. We have used gene-modification of allogeneic tumor cell lines to create generic RCC vaccines. More recently, emphasis has shifted to the use of DCs as cell-based vaccines for RCC. DCs have moved to a position of central interest because of their excellent stimulatory capacity, combined with their ability to process and present antigens to both naive CD4 and CD8 cells. The long impasse in identifying molecular targets for specific immunotherapy of RCC is now rapidly being overcome through the use of tools and information emerging from human genome research. Identification of candidate molecules expressed by RCC using cDNA arrays, combined with protein arrays and identification of peptides presented by MHC molecules, allow specific vaccines to be tailored to the antigenic profile of individual tumors, providing the basis for development of patient-specific vaccines.
Frankenberger
Bernhard
B
Institute of Molecular Immunology, GSF-National Research Center for Environment and Health, Marchioninistrasse 25, 81377 Munich, Germany, b.frankenberger@gsf.de
Regn
Sybille
S
Geiger
Christiane
C
Noessner
Elfriede
E
Falk
Christine S
CS
Pohla
Heike
H
Javorovic
Miran
M
Silberzahn
Tobias
T
Wilde
Susanne
S
Buchner
Alexander
A
Siebels
Michael
M
Oberneder
Ralph
R
Willimsky
Gerald
G
Pezzutto
Antonio
A
Blankenstein
Thomas
T
Schendel
Dolores J
DJ
D019496:Cancer Vaccines / Q000235:genetics / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000628:therapy*; D003713:Dendritic Cells / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007680:Kidney Neoplasms / Q000628:therapy*; D009000:Monocytes / Q000166:cytology
D019496:Cancer Vaccines