Immunogenicity of recombinant GA733-2E antigen (CO17-1A, EGP, KS1-4, KSA, Ep-CAM) in gastro-intestinal carcinoma patients.
Targeting the GA733 antigen (also known as CO17-1A, EGP, KS1-4, KSA, Ep-CAM) by monoclonal antibody CO17-1A or anti-idiotypic antibodies mimicking the CO17-1A or GA733 epitope has induced prolonged survival and specific immune responses to the antigen, respectively, in colorectal cancer (CRC) patients. In pre-clinical studies in mice and rabbits, recombinant baculovirus-derived GA733-2E antigen was superior to anti-idiotypic antibodies at modulating specific immune responses. Our aim was to evaluate the immunogenicity and potential toxicity of alum-precipitated GA733-2E in a phase I trial in patients with resected CRC or pancreatic cancer. Six patients with advanced pancreatic carcinoma and 6 with CRC Dukes' stage A, B or C received between 4 and 7 doses of alum-precipitated GA733-2E at 50, 200 or 800 microg/dose at monthly intervals. Antibody binding to GA733-2E or antigen-positive CRC cells was determined, as were antigen-specific proliferative, cytolytic T-lymphocyte and delayed-type hypersensitivity responses. Six of the 12 patients developed antigen-specific humoral immune responses after immunotherapy, and 8 developed cellular immune responses. The overall immune response rate, including patients with humoral and/or cellular immune responses, was 83%. Median overall survival of the CRC and pancreatic cancer patients was 39.8 and 11.2 months, respectively. Following 18 years of single-epitope targeting of the GA733 antigen, immunization of patients against multiple epitopes of the antigen frequently induces an immune response in the absence of significant toxicity, despite relatively widespread expression of this antigen on normal epithelial cells.
Department of Surgery, University of Ulm, Germany.
L
L
Staib
B
B
Birebent
R
R
Somasundaram
E
E
Purev
H
H
Braumüller
C
C
Leeser
N
N
Küttner
W
W
Li
D
D
Zhu
J
J
Diao
W
W
Wunner
D
D
Speicher
H G
HG
Beger
H
H
Song
D
D
Herlyn
D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology; D000917:Antibody Formation; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology / Q000628:therapy; D016207:Cytokines / Q000032:analysis; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D006968:Hypersensitivity, Delayed; D007111:Immunity, Cellular; D007167:Immunotherapy; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000628:therapy; D011994:Recombinant Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015815:Cell Adhesion Molecules; D016207:Cytokines; D000071858:Epithelial Cell Adhesion Molecule; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic