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Báo cáo khoa học: Human anti-ErbB2 immunoagents – immunoRNases and compact antibodies

Immunotherapy, based on mAbs specifically directed against cancer cells, is considered a precious strategy in the fight against cancer because of its selec-tivity and lack of multidrug resistant effects. However, there are obstacles to the complete success of current immunotherapy such as immune responses to nonhuman or even humanized antibodies and the large size of the anti-bodies, which hinders their diffusion into bulky tumors. | ỊFEBS Journal REVIEW ARTICLE Human anti-ErbB2 immunoagents - immunoRNases and compact antibodies Claudia De Lorenzo and Giuseppe D Alessio Dipartimento di Biologia Strutturale e Funzionale Universita di Napoli Federico II Italy Keywords antibodies antitumor drugs breast cancer cardiotoxicity ErbB2 herceptin immunoagents immunogenicity immunoRNases immunotherapy Correspondence C. De Lorenzo Dipartimento di Biologia Strutturale e Funzionale University di Napoli Federico II Via Cinthia 80126 Naples Italy Fax 39 081 67 9159 Tel 39 081 67 9158 E-mail cladelor@unina.it Received 11 December 2008 revised 8 January 2009 accepted 9 January 2009 doi 10.1111 j.1742-4658.2009.06896.x Immunotherapy based on mAbs specifically directed against cancer cells is considered a precious strategy in the fight against cancer because of its selectivity and lack of multidrug resistant effects. However there are obstacles to the complete success of current immunotherapy such as immune responses to nonhuman or even humanized antibodies and the large size of the antibodies which hinders their diffusion into bulky tumors. Fully human small immunoagents capable of inhibiting tumor growth may overcome these problems and provide safe highly selective and effective antitumor drugs. An attractive target for immunotherapy is ErbB2 a transmembrane tyrosine kinase receptor overexpressed on tumor cells of different origin with a key role in the development of malignancy. An anti-ErbB2 humanized monoclonal Herceptin is currently used with success for breast cancer therapy however it can engender cardiotoxicity and a high proportion of breast cancer patients are resistant to Herceptin treatment. Anti-ErbB2 immunoagents of human origin with potentially no or very low immunogenicity have been engineered to assemble compact i.e. reduced size antibodies one consisting of a human single-chain antibody fragment scFv fused to a human RNase to construct an immunoRNase and the other made up of two human scFv .