MAb17-1A and cytokines for the treatment of patients with colorectal carcinoma.
CO17-1A/GA73-3/EpCam/KSA is a cellular adhesion molecule expressed on the majority of tumor cells in most patients with colorectal carcinoma. One of the first mouse monoclonal antibodies (MAbs) for therapeutic use was produced against this particular tumor associated antigen (MAb17-1A). MAb17-1A has served as a model for the development of antibody therapy. It exerts therapeutic effects through antibody dependent cellular cytotoxicity (ADCC), induction of an idiotypic network cascade and maybe also by complement activation. Addition of cytokines that augment these functions, mainly granulocyte macrophage-cerebrospinal fluid (GM-CSF), seemed to improve the clinical efficacy as well as chemotherapeutic agents (5-Fu). In advanced disease the clinical effect is, however, modest while the most beneficial clinical situation seems to be the adjuvant setting. Twenty years have passed since the EpCam antigen was identified as a target structure for immunotherapy, but still we do not know how to optimally use this target. The antigen might, however, be a rewarding structure to utilize for therapy. Preclinical and clinical trials are ongoing aimed at improving passive and active immunotherapy using CO17-1A/EpCam as a target antigen in colorectal carcinoma.
Frödin
Jan-Erik
JE
Department of Oncology (Radiumhemmet), Division of Oncologic Biotherapy, CancerCentrumKarolinska, Karolinska Hospital, Stockholm, Sweden.
Fagerberg
Jan
J
Hjelm Skog
Anna-Lena
AL
Liljefors
Maria
M
Ragnhammar
Peter
P
Mellstedt
Håkan
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000276:immunology / Q000628:therapy*; D016207:Cytokines / Q000627:therapeutic use*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use; D051379:Mice
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D016207:Cytokines; D016898:Interferon-alpha; D007376:Interleukin-2; C050928:carcinoma-associated antigen 17-1A; C400149:Edrecolomab; D016178:Granulocyte-Macrophage Colony-Stimulating Factor