Possible targets on carcinoma for bMAb retargeting of lymphocyte or drug cytotoxicity.
Retargeting of drugs or lymphocyte cytotoxicity through bi-specific monoclonal antibodies (bMAbs) has been proven a therapeutic tool against human carcinoma both in pre-clinical in vitro and in vivo studies. Some of these reagents have already been introduced into clinical trials and preliminary results appear to be promising. However, improvement of the specificity of this approach could be achieved by selecting more suitable target molecules on tumor cells. The research focused on developing MAbs directed against molecules with tumor-restricted distribution and homogeneous expression. Cell-membrane receptors for nutrients or growth factors which operationally represent tumor-specific molecules due to their overexpression, could be considered appropriate targets. Several bMAb anti-nutrients (the folate-binding protein) or growth-factor receptor (c-erbB1, c-erbB2)/anti-triggering molecules have been generated and all were able to efficiently retarget the relevant population of lymphocytes on tumor cells. In order to design a more reliable and selective therapeutic tool, the following parameters were analyzed: correlation between cytotoxicity and antigen level, potency and possible modulation of the target molecule.
Canevari
S
S
Istituto Nazionale Tumori, Milan, Italy.
Mezzanzanica
D
D
Ménard
S
S
Ferrini
S
S
Moretta
L
L
Colnaghi
M I
MI
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity; D015703:Antigens, CD / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007167:Immunotherapy; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000951:Antigens, Neoplasm