Antibodies increasing potency

Immunotoxins continue to be actively investigated as viable alternatives to conventional therapies for a variety of diseases. An array of different recombinant, antibody formats are now available for use in immunotoxins. While these design changes have improved the overall in vitro and preclinical in vivo efficacy of immunotoxins, increased potency does not address either of the two major concerns for drugs of this type immunogenicity and toxicity. As such, immunotoxins in their current form may have limited application other than to those disease conditions either where the patients are immunocompro-... 

Engineered IgG antibodies have been constructed with altered affinity to human Fey receptors and altered potency in vitro and in animal models [14, 31-33]. Mutations of critical residues in the Fc region (CH2 domain or the hinge region joining CH1 and CH2) have enhanced or decreased antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) [33-37]. In addition, alterations in residues located at the CH2 domain of I gC, i involved in binding with Clq protein, a component of the complement activation cascade, resulted in a significant increase in CDC activity [34, 35]. 

M., Addition of an extra immunoglobulin domain to two anti-rodent TNF monoclonal antibodies substantially increased their potency. Mol. Immunol. 41, 73-80, 2004 Adams, G.P., Tai, M.S., McCartney, J.E. et al.. Avidity-mediated enhancement of in vivo tumor targeting by single-chain Fv dimers, Clin. Cancer Res. 12, 1599-1605, 2006. 

The approach behind the development of ADCs as oncology therapeutics is to combine the selectivity of an antibody toward tumor antigens with the potency of a cytotoxic agent in an effort to increase target specificity and reduce systemic... 

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