Monoclonal Antibodies for the Immunotherapy of Solid Tumours

Richard      Mauerer; Rudolf      Gruber

Abstract

More than 80% of all cancers are caused by solid malignancies. More than 90% of these tumours are of epithelial origin. The main principles in tumour treatment are surgery, radiotherapy, chemotherapy or combinations of these. Complete surgical removal of the tumour is the most effective therapy for solid malignancies. Recent advances in early cancer detection led to a higher rate of resectable primary tumours and therefore prognosis will be determined especially by metastasis. Even in early stages some tumour cells may disseminate for example into the bone marrow. If these occult metastasis get evident they are mostly incurable by surgery and often highly resistant to chemotherapy. Developing new therapeutic agents to destroy these resting cells is a major challenge for the improvement of cancer therapy in the future. Advances to reach these goals were made in immunological therapies with monoclonal antibodies (MABs). These MABs are for example directed against tumor-associated antigens (TAAs). By binding selectively on tumor cells they can activate immunological effector mechanisms, e.g. antibody dependent cell cytotoxicity (ADCC) or complement mediated lysis. Other mechanisms are the blocking of inhibiting molecules to re-activate anergic tumor infiltrating lymphocytes (TILs). Furthermore growing tumours depend on oxygen supply, i.e. on effective neovascularisation. Antibodies against VEGF are able to inhibit neovascularisation and are therefore used successfully in tumour therapy.

Keywords: Micro metastasis, tumour-associated antigen (TAA), antibody-dependent cell cytotoxicity (ADCC), complementmediated lysis, tumour-infiltrating lymphocytes (TIL), solid malignancies, radiotherapy, chemotherapy, bone marrow, primary tumours, tumour cells, resting cells, cancer therapy