Pre-clinical evaluation of a CEA DNA prime/protein boost vaccination strategy against colorectal cancer.
In preparation for a clinical trial in patients diagnosed with colorectal cancer, a vaccination strategy targeting the carcinoembryonic antigen (CEA) was evaluated in mice using a GMP-produced plasmid DNA vaccine, CEA66, encoding a truncated form of the tumour-associated antigen, CEA. The GMP-produced CEA DNA vaccine was also evaluated for toxicity. Repeated intradermal administration of the GMP-produced vaccine using a novel needle-free jet injection device (Biojector) induced robust CD4 and CD8 T-cell responses in mice, and did not result in any vaccine-related toxicity. In a heterologous DNA prime/protein boost setting, cellular immune responses were of higher magnitude in animals primed with CEA66 DNA than in animals receiving repeated doses of recombinant CEA protein. These responses were further enhanced if recombinant murine granulocyte-macrophage colony-stimulating factor was given as an adjuvant prior to vaccination. In contrast to repeated administration of recombinant CEA protein as a single modality vaccine, the heterologous CEA66 DNA prime/rCEA boost vaccination strategy resulted in a qualitatively broader immune response, and supports clinical testing of this vaccination regimen in humans.
Hallermalm
K
K
Department of Microbiology and Tumor and Cell Biology, Karolinska Institutet & Swedish Institute for Infectious Disease ControlCenter for Molecular Medicine, Karolinska InstitutetVecura, Cell & Gene Therapy Center, Karolinska SjukhusetCancer Center Karolinska, Karolinska Sjukhuset, Stockholm, SwedenBioject Medical Technologies Inc., Tualatin, OR, USAProTherImmune, Lafayette, CA, USA.
Johansson
S
S
Department of Microbiology and Tumor and Cell Biology, Karolinska Institutet & Swedish Institute for Infectious Disease ControlCenter for Molecular Medicine, Karolinska InstitutetVecura, Cell & Gene Therapy Center, Karolinska SjukhusetCancer Center Karolinska, Karolinska Sjukhuset, Stockholm, SwedenBioject Medical Technologies Inc., Tualatin, OR, USAProTherImmune, Lafayette, CA, USA.
Bråve
A
A
Department of Microbiology and Tumor and Cell Biology, Karolinska Institutet & Swedish Institute for Infectious Disease ControlCenter for Molecular Medicine, Karolinska InstitutetVecura, Cell & Gene Therapy Center, Karolinska SjukhusetCancer Center Karolinska, Karolinska Sjukhuset, Stockholm, SwedenBioject Medical Technologies Inc., Tualatin, OR, USAProTherImmune, Lafayette, CA, USA.
Ek
M
M
Department of Microbiology and Tumor and Cell Biology, Karolinska Institutet & Swedish Institute for Infectious Disease ControlCenter for Molecular Medicine, Karolinska InstitutetVecura, Cell & Gene Therapy Center, Karolinska SjukhusetCancer Center Karolinska, Karolinska Sjukhuset, Stockholm, SwedenBioject Medical Technologies Inc., Tualatin, OR, USAProTherImmune, Lafayette, CA, USA.
Engström
G
G
Department of Microbiology and Tumor and Cell Biology, Karolinska Institutet & Swedish Institute for Infectious Disease ControlCenter for Molecular Medicine, Karolinska InstitutetVecura, Cell & Gene Therapy Center, Karolinska SjukhusetCancer Center Karolinska, Karolinska Sjukhuset, Stockholm, SwedenBioject Medical Technologies Inc., Tualatin, OR, USAProTherImmune, Lafayette, CA, USA.
Boberg
A
A
Department of Microbiology and Tumor and Cell Biology, Karolinska Institutet & Swedish Institute for Infectious Disease ControlCenter for Molecular Medicine, Karolinska InstitutetVecura, Cell & Gene Therapy Center, Karolinska SjukhusetCancer Center Karolinska, Karolinska Sjukhuset, Stockholm, SwedenBioject Medical Technologies Inc., Tualatin, OR, USAProTherImmune, Lafayette, CA, USA.
Gudmundsdotter
L
L
Department of Microbiology and Tumor and Cell Biology, Karolinska Institutet & Swedish Institute for Infectious Disease ControlCenter for Molecular Medicine, Karolinska InstitutetVecura, Cell & Gene Therapy Center, Karolinska SjukhusetCancer Center Karolinska, Karolinska Sjukhuset, Stockholm, SwedenBioject Medical Technologies Inc., Tualatin, OR, USAProTherImmune, Lafayette, CA, USA.
Blomberg
P
P
Department of Microbiology and Tumor and Cell Biology, Karolinska Institutet & Swedish Institute for Infectious Disease ControlCenter for Molecular Medicine, Karolinska InstitutetVecura, Cell & Gene Therapy Center, Karolinska SjukhusetCancer Center Karolinska, Karolinska Sjukhuset, Stockholm, SwedenBioject Medical Technologies Inc., Tualatin, OR, USAProTherImmune, Lafayette, CA, USA.
Mellstedt
H
H
Department of Microbiology and Tumor and Cell Biology, Karolinska Institutet & Swedish Institute for Infectious Disease ControlCenter for Molecular Medicine, Karolinska InstitutetVecura, Cell & Gene Therapy Center, Karolinska SjukhusetCancer Center Karolinska, Karolinska Sjukhuset, Stockholm, SwedenBioject Medical Technologies Inc., Tualatin, OR, USAProTherImmune, Lafayette, CA, USA.
Stout
R
R
Department of Microbiology and Tumor and Cell Biology, Karolinska Institutet & Swedish Institute for Infectious Disease ControlCenter for Molecular Medicine, Karolinska InstitutetVecura, Cell & Gene Therapy Center, Karolinska SjukhusetCancer Center Karolinska, Karolinska Sjukhuset, Stockholm, SwedenBioject Medical Technologies Inc., Tualatin, OR, USAProTherImmune, Lafayette, CA, USA.
Liu
M A
MA
Department of Microbiology and Tumor and Cell Biology, Karolinska Institutet & Swedish Institute for Infectious Disease ControlCenter for Molecular Medicine, Karolinska InstitutetVecura, Cell & Gene Therapy Center, Karolinska SjukhusetCancer Center Karolinska, Karolinska Sjukhuset, Stockholm, SwedenBioject Medical Technologies Inc., Tualatin, OR, USAProTherImmune, Lafayette, CA, USA.
Wahren
B
B
Department of Microbiology and Tumor and Cell Biology, Karolinska Institutet & Swedish Institute for Infectious Disease ControlCenter for Molecular Medicine, Karolinska InstitutetVecura, Cell & Gene Therapy Center, Karolinska SjukhusetCancer Center Karolinska, Karolinska Sjukhuset, Stockholm, SwedenBioject Medical Technologies Inc., Tualatin, OR, USAProTherImmune, Lafayette, CA, USA.
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000494:pharmacology; D006157:Guanosine Monophosphate / Q000276:immunology; D006367:HeLa Cells; D006801:Humans; D007277:Injections, Jet; D051379:Mice; D010957:Plasmids; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection; D019076:Transgenes; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology / Q000633:toxicity
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006157:Guanosine Monophosphate