Yesterday, GEN published a nice article on antibody drug conjugates (ADC) and their increasing use in cancer therapy. The article used anti-CD30 antibodies coupled to monomethyl auristatin E as one such example. This ADC by Seattle Genetic's also known as brentuximab vedotin can be used to treat patients with Hodgkins lymphoma (note: NOT non-Hodgkins B-cell lymphoma), various T-cell lymphoma's and some other hematologic-derived cancers - all of which express the CD30 antigen. PharmTech also did a nice article (2007) summarizing this area as well as outlining a number of the major pharma players active with ADC programs.
The ADC concept allows the clinician to very specifically target cancer cells that express antigens not expressed by normal tissues and to couple the cytotoxic reagent to the antibody providing this exquisite targetting. Thus, a chemotherapeutic payload can be delivered specifically to a cancer cell. This has been particularly useful to many patients who have not responded to other more traditional radiation or chemotherapy regimes in clinical trials to date.
Another example of the ADC concept is Roche's (Genentech) TDM1 therapy - a Herceptin antibody coupled to a chemotherapy agent. TDM1 has had success in clinical with women who have Her-2 positive breast cancer and who have not responded to other chemotherapy regimes. In a recent study, these women may have seen as many as 7 chemotherapeutic agents prior to their ADC treatment.
Thus ADC's are seen as a new generation of therapeutic compound that can be used to provide the next round of anti-cancer therapies.
Challenges Creating ADCs
One of the challenges in creating ADC's is the need to provide the linker chemistry that gives the ADC complex stability in the bloodstream yet allows release of the chemotherapeutic payload at the target cancer cell. This must also be done in a way that you do not adversely impact the antibody's binding capability or its ability to be internalized to deliver a drug payload. Once it is internalized, the ADC has to release the chemotherapeutic agent to be effective. See recent review article.
You need good chemistry to create ADCs. The SAFC Pharma group has developed the conjugation chemstry necessary to allow us to conjugate biological molecules (including antibodies) to high-potent APIs (HPAPI) to meet pharmaceutical industry demands. We have been providing this type of expertise for more than 15 years and can now support manufacturing of ADCs from pre-clinical to commercial scale. See our website for more on Bioconjugation.
My next post will continue this discussion and highlight new SAFC facilities for manufacture of HPAPIs and ADCs.
Posted by Bruce Lehr March 3, 2010