Monoclonal antibody for cancer immunotherapy has become established over the past 15 years and is now one of the most successful and important strategies for treating patients with haematological malignancies and solid tumours.
Monoclonal antibody functions in cancer immunotherapy more than three ways, targeting cancer associated antigen and immune modulating molecules:
(1) Monoclonal antibody kill tumor directly (through receptor blockade or agonist activity, induction of apoptosis, or delivery of a drug or cytotoxic agent). Cetuximab, for instance, a chimeric EGFR-specific IgG1 monoclonal antibody, functions by preventing binding of activating ligand and by preventing receptor dimerization, a crucial step for initiating EGFR-mediated signal transduction.
(2) Immune-modulated cell killing mechanisms (including, complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and regulation of T cell function). Many tumours have been shown to express CD40, including carcinomas of the ovary, nasopharynx, bladder, cervix, breast and prostate, and the engagement of CD40 can lead to a direct antitumour effect in some tumours in vivo. In one study, the effect of a fully human CD40-specific agonist monoclonal IgG2 was assessed in 29 patients with advanced solid tumours. The results showed four partial responses (all patients with melanoma) and one complete resolution.
(3) Specific effects of monoclonal antibody on tumour vasculature and stroma. Bevacizumab, a VEGFA-specific humanized monoclonal antibody, blocks binding of VEGF to its receptor and is approved for the treatment of breast, colorectal and non-small-cell lung cancer in combination with cytotoxic chemotherapy.
Since 1997, more than 10 antibodies have received approval from the FDA for the cancer immunotherapy of various solid tumours and haematological malignancies, such as monoclonal antibodies for ERBB2, VEGF, EGFR, CTLA4, CD20, CD52, CD33, and CD30, and a large number of additional therapeutic antibodies are currently being tested in early stage and late-stage clinical trials. With the development of combining monoclonal antibody for cancer immunotherapy with other therapy method, More and more afficacies will be achieved.
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