Two novel human antitumor immunoconjugates, engineered by fusion of a
single-chain antibody fragment against human ErbB2 receptor, termed
Erbicin, with either a human RNase or the Fc region of a human IgG1
are selectively cytotoxic for ErbB2-positive cancer cellsin vitro andin vivo.
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.
Overexpression of the ErbB2 receptor is associated with the progression of
breast cancer, and is a sign of a poor prognosis. Herceptin, a humanized
antibody directed to the ErbB2 receptor, has been proven to be effective in
the immunotherapy of breast cancer. However, it can result in cardiotoxicity,
and a large fraction of breast cancer patients are resistant to Herceptin treat-ment.