| Melvyn Little at Affimed Therapeutics AG explores the discovery and development of antibody treatments specifically targeting difficult cancers
Monoclonal antibodies (MAbs) are now an established category of therapeutic agents for targeted cancer therapy. Early research, which related to the treatment of haematologic malignancies, was impressive, and euphoria about these targeted medicines rose, with a general assumption in the scientific community that nearly every cancer could easily be treated in the future. Less than 30 years later, a number of MAb therapeutics to target tumour cells have reached the market. However, the reality is that while MAbs have proved useful, there are drawbacks to their use and they are yet to be the panacea that was originally anticipated.
For a start, the discovery process of new MAbs for cancer treatment remains extremely expensive and time consuming. In addition, the manufacture of these large and delicate proteins in mammalian hosts is expensive and not easily scaleable. Rituximab (Biogen Idec/Genentech and Roche), a monoclonal antibody used in the treatment of B cell non-Hodgkin’s lymphoma, B cell leukemia, and some autoimmune disorders, costs around ˆ13,000 per patient (1).
Such costs mean antibody treatments cannot be provided to a large number of patients who might otherwise benefit. A further drawback is that, while MAbs demonstrate exquisite selectivity for tumour cells, leading to reduced collateral damage to non-cancerous tissue when compared with cytotoxic chemotherapy, they still commonly exhibit unwanted side effects such as immunogenicity or activation of other parts of the immune system, such as the complement cascade.
Part of the reason for this is the fact that MAbs are large proteins, but also because many of the first generation MAbs are of murine origin. Immunogenicity leads to the direct destruction by the patient’s immune system of a vast amount of the precious MAbs shortly after injection. This effect lessens the therapeutic effectiveness of the treatment and means that relatively high doses of MAb treatments are often necessary to guarantee a therapeutic effect. |
