Antibodies designed as effective cancer vaccines.
Antigen/antibody complexes can efficiently target antigen presenting cells to allow stimulation of the cellular immune response. Due to the difficulty of manufacture and their inherent instability complexes have proved inefficient cancer vaccines. However, anti-idiotypic antibodies mimicking antigens have been shown to stimulate both antibody and T cell responses. The latter are due to T cell mimotopes expressed within the complementarity-determining regions (CDRs) of antibodies that are efficiently presented to dendritic cells in vivo. Based on this observation we have designed a DNA vaccine platform called ImmunoBody, where cytotoxic T lymphocyte (CTL) and helper T cell epitopes replace CDR regions within the framework of a human IgG1 antibody. The ImmunoBody expression system has a number of design features which allow for rapid production of a wide range of vaccines. The CDR regions of the heavy and light chain have been engineered to contain unique restriction endonuclease sites, which can be easily opened, and oligonucleotides encoding the T cell epitopes inserted. The variable and constant regions of the ImmunoBody are also flanked by restriction sites, which permit easy exchange of other IgG subtypes. Here we show a range of T cell epitopes can be inserted into the ImmunoBody vector and upon immunization these T cell epitopes are efficiently processed and presented to stimulate high frequency helper and CTL responses capable of anti-tumor activity.
Metheringham
R L
RL
Scancell Limited, Department of Clinical Oncology, University of Nottingham, Nottingham, UK.
Pudney
V A
VA
Gunn
B
B
Towey
M
M
Spendlove
I
I
Durrant
L G
LG
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D022801:Complementarity Determining Regions / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors / Q000276:immunology; D006801:Humans; D007115:Immunization Schedule; D007074:Immunoglobulin G / Q000276:immunology; D007271:Injections, Intradermal; D008213:Lymphocyte Activation; D008546:Melanoma, Experimental / Q000517:prevention & control / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use
D000888:Antibodies, Anti-Idiotypic; D019496:Cancer Vaccines; D022801:Complementarity Determining Regions; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; D019444:Vaccines, DNA