Antibody-based cancer therapies: back to “polyclonals”?

Excerpt

The Paul Ehrlich concept of tumour targeting with antibodies directed towards tumour-specific antigens is more than a century old [1]. Nevertheless, the modern era of targeted cancer therapy did not start until 1975, upon the publication of Kohler and Milstein’s work describing the technology for the production of monoclonal antibodies (MoAbs) [2]. After two decades of fluctuation in the international interest in research into, and development of, MoAbs, the clinical success of anti-tumour antibodies like rituximab (IDEC, Roche, 1997) and Herceptin (Genentech, Roche, 1998) gave new and vigorous impetus to the field. By February 2004, eight MoAbs had been approved for cancer therapy, and these represent just the tip of the iceberg as dozens of other antibodies are currently under investigation worldwide, accounting for 30% of all biopharmaceuticals in clinical trials. Over the years, antibody selection has been based on identification of tumour-specific antigens in order to avoid the systemic toxicity seen with synthetic drugs. It is to be noted that five out of the eight above-mentioned registered MoAbs are indicated for the therapy of haematological tumours. This is no coincidence, for these tumours are more easily accessible than solid tumours and their antigen expression is also more consistent. …