Each of the components of an ADC, as well as their interaction as a system, must be optimized to achieve an effective, well-tolerated ADC.
Our purpose-developed cytotoxic payload agents are much more potent than traditional chemotherapy. We have tubulin-acting payloads (e.g., DM1, DM4), which are maytansinoids, and DNA-acting payloads (e.g., DGN462), which we call IGNs.
The importance of understanding the target itself is precedent to the development of an ADC. Our scientists have expertise in target selection, including assessment of appropriate levels on tumor vs. normal tissue and rate of internalization.
We have established expertise in the development of tumor-targeting antibodies. We created one of the few CD37-targeting antibodies known.
We have developed engineered linkers (e.g., SMCC, SPDB, S-SPDB) that are designed to be stable while the ADC is traveling to the tumor and then optimize payload efficacy once inside a cancer cell.
- ADC illustrations typically show release of the cytotoxic payload in the lysosome (A). This occurs because lysosomal enzymes there digest away the antibody part of the ADC. For ADCs with ImmunoGen technology, the released payload is fully active, with the linker still attached.
- With some targets, there is poor trafficking to the lysosome. ImmunoGen scientists have created linkers that are stable outside the cancer cell but able to break, or “cleave”, once inside the cell (B), providing another route to payload release.
- With ImmunoGen “cleavable” linkers, released payload is also able to enter a neighboring cancer cell and kill it (C). This can enhance the tumor-killing ability of an ADC.
Last updated: January 5, 2015