Ga733/EpCAM as a target for passive and active specific immunotherapy in patients with colorectal carcinoma.
GA733/EpCAM is an oncofetal antigen abundantly expressed in colorectal carcinoma. This antigen can spontaneously induce a humoral and cellular antitumor immunity and may therefore be a suitable target structure for immunotherapy. Patients with advanced colorectal carcinoma have been treated with monoclonal antibodies (MAb17-1A) against this structure. The data indicate that the chimeric variant was not superior to the original mouse MAb. Addition of cytokines and chemotherapeutics may improve the therapeutic effect of the MAb. A particularly interesting regimen is a combination of MAb17-1A/GM-CSF/alpha-IFN/5-Fu. The GA733 protein antigen can also be used as a vaccine. Patients with colorectal carcinoma stages B and C were vaccinated with this protein antigen in combination with GM-CSF as an adjuvant cytokine. A strong type I T cell response was induced that seemed to be MHC class I as well as class II restricted. No systemic side effects were noted.
Cancer Centre Karolinska, Department of Oncology, Karolinska Hospital/Karolinska Institute, Stockholm, Sweden. hme@rah.ks.se
H
H
Mellstedt
J
J
Fagerberg
J E
JE
Frödin
A L
AL
Hjelm-Skog
M
M
Liljefors
K
K
Markovic
S
S
Mosolits
P
P
Ragnhammar
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000276:immunology / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology; D000071858:Epithelial Cell Adhesion Molecule; D006801:Humans; D007167:Immunotherapy; D051379:Mice; D016019:Survival Analysis
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule