Low doses of 105AD7 cancer vaccine preferentially stimulate anti-tumor T-cell immunity.
Clinical studies with the human anti-idiotypic antibody 105AD7 have clearly shown that 791Tgp72 is a good target antigen for cell-mediated immunity. No antibody-related toxicity was observed in any of the 135 patients entered into phase I/II clinical trials of 105AD7, whereas both helper and cytotoxic T-cell responses were induced. The helper responses were exemplified by induction of interleukin-2 (IL-2), antigen-specific blastogenesis, and enhanced natural killer (NK) activity. Anti-tumor cytotoxicity was measured directly and was supported by activation of circulating CD8 cells. In this study, it is shown that a 100-microgram injection of 105AD7 was more effective than the 200-microgram dose. Enhanced IL-2 production was observed following 15/19 injections of 100 micrograms of 105AD7 whereas only 4/11 injections of 200 micrograms of 105AD7 induced responses (p < 0.02). Similarly, time to progression was significantly (p < 0.05) slower (median 6 m) in patients injected with 100 micrograms than patients receiving the higher dose, suggesting that 100 micrograms or lower may be the optimal dose. The standard dose for hepatitis vaccination is 10 micrograms. In vitro blastogenesis assays on naive donors have shown that a dose of 105AD7, which is either too high or too low, fails to activate T cells. The optimal dose in vitro is 10 ng.
Durrant
L G
LG
CRC Department of Clinical Oncology, Nottingham University, UK.
Buckley
D J
DJ
Spendlove
I
I
Robins
R A
RA
D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology / Q000628:therapy; D018450:Disease Progression; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines