Monoclonal antibodies (mAbs) have demonstrated considerable utility in cancer treatment. There are a number of unmodified mAbs currently available for patient treatment, including Rituxan (non-Hodgkin's lymphoma), Erbitux (colorectal carcinoma), Herceptin (metastatic breast cancer), and Avastin (colorectal cancer). In order to improve the therapeutic value of mAbs, considerable effort is now being focused on enhancing their activity by attaching cytotoxic drugs to the biomolecules. This combination of small molecule drugs and antigen specific biomolecules results in a targeted system for drug delivery, an antibody-drug conjugate (ADC). However, many ADCs in development have had issues with variable potency as well as toxicity, in particular, hepatotoxicity. A significant obstacle to the creation of a successful modified ADC therapeutic is the need to produce the conjugated product in a homogenous form with a defined and controlled toxic payload. However, the existing methods for chemical protein modification result in mixtures of product, with varying amounts of toxin conjugated to the peptide backbone. We have developed a technology platform that modifies proteins in a controlled, site-specific manner. This technology can generate a modified recombinant IgG that has homogenous attachment sites and is easy to chemically elaborate, resulting in a conjugated antibody coupled to a defined amount of drug. If successful, we believe this work will change the utility of ADC therapeutics and will result in a robust pipeline of best in class biotherapeutics.
The combination of small molecule drugs and antigen specific biomolecules results in a targeted system for drug delivery, an antibody-drug conjugate (ADC). Redwood Bioscience's aldehyde-tagged technology can generate a novel, modified recombinant ADC. We believe this work will change the utility of ADC therapeutics and will result in a robust pipeline of best in class biotherapeutics.
|Drake, Penelope M; Albers, Aaron E; Baker, Jeanne et al. (2014) Aldehyde tag coupled with HIPS chemistry enables the production of ADCs conjugated site-specifically to different antibody regions with distinct in vivo efficacy and PK outcomes. Bioconjug Chem 25:1331-41|