Antibodies have long been recognized as selective and effective targeting vehicles of diagnostic and therapeutic radionuclides for imaging or radiotherapy applications, such as cancer. A major challenge is to enhance the nuclear radiation delivered to the target while minimizing radiation uptake in other tissues. Antibodies circulate for a long time, which leads to poor target-to-nontarget ratios in imaging procedures and to radiation dose-limiting side effects in healthy organs in therapy procedures. As a result, solid tumors have remained out of reach of radioimmunotherapy, and today still represent a high unmet clinical need.
Pretargeting – Our Proprietary Solution
Tagworks’ technology improves the effectiveness of radioimmunoimaging and -therapy through boosting target-to-nontarget ratios and enabling repeat treatments. This is achieved by “pretargeting”, which centers on target binding of a tagged antibody followed by binding of a small, fast-clearing, radiolabeled probe to the tag of the target-bound antibody in a second step. Usually, freely circulating antibody is cleared to the liver by injection of a clearing agent prior to probe injection. The resulting superior ratios enable effective imaging and allow the administration of much higher amounts of therapeutic radioactivity, increasing efficacy.
Other pretargeting systems use biological interactions (streptavidin-biotin, antibody-hapten) to recruit the probe to the target-bound antibody, but suffer from immunogenicity and/or involve extensive reengineering and perturbation of the parent antibody. Tagworks’ chemical approach is based on the fastest and highly selective click reaction, the inverse-electron-demand-Diels-Alder reaction. The components are less likely to give rise to immunogenicity, potentially allowing treatment fractionation, which has proven critical to maximize the efficacy for other cancer treatment modalities. In addition, the small tag leads to minimal pertubation of the tagged antibody, making the approach ideally suited for companion imaging applications in (pre)clinical antibody development.