The demonstration that targeting MUC1-C is an effective therapeutic approach for cancer treatment has emphasized the importance of developing other agents that are directed against this oncoprotein.
Early attempts at targeting MUC1 that focused on the development of MAbs against MUC1-N were unsuccessful largely because this subunit is shed from the cancer cell surface. Other MAbs have been developed that react with MUC1-N at the junction with MUC1-C. In contrast to MUC1-N, the MUC1-C subunit is not shed; in this regard and to our knowledge, there are no MAbs that react with the MUC1-C 58-aa extracellular domain, other than the novel clones we have developed that bind selectively to this region. These high affinity antibodies react with the surface of MUC1-C-expressing cancer cells and undergo internalization, a process of importance for the intracellular delivery of therapeutic agents and GO-203/NPs.
The generation of MAbs against the MUC1-C extracellular domain (MUC1-C/ED) provides an opportunity for developing novel therapeutic approaches that target MUC1-C on the surface of cancer cells. In this way, there are multiple potential applications for MAbs that bind to cell surface proteins:
Our work has focused in part on the development of ADCs, based in part on the preliminary findings that these conjugates are effective in killing cancer cells growing in vitro and as xenografts in nude mice.
Early attempts at targeting MUC1 that focused on the development of MAbs against MUC1-N were unsuccessful largely because this subunit is shed from the cancer cell surface. Other MAbs have been developed that react with MUC1-N at the junction with MUC1-C. In contrast to MUC1-N, the MUC1-C subunit is not shed; in this regard and to our knowledge, there are no MAbs that react with the MUC1-C 58-aa extracellular domain, other than the novel clones we have developed that bind selectively to this region. These high affinity antibodies react with the surface of MUC1-C-expressing cancer cells and undergo internalization, a process of importance for the intracellular delivery of therapeutic agents and GO-203/NPs.
The generation of MAbs against the MUC1-C extracellular domain (MUC1-C/ED) provides an opportunity for developing novel therapeutic approaches that target MUC1-C on the surface of cancer cells. In this way, there are multiple potential applications for MAbs that bind to cell surface proteins:
- antibody-drug conjugates (ADCs)
- antibody-dependent cellular cytotoxicity (ADCC)
- complement-mediated cytotoxicity (CMC)
- bispecific antibodies
- CAR-T or CAR-NK cells
Our work has focused in part on the development of ADCs, based in part on the preliminary findings that these conjugates are effective in killing cancer cells growing in vitro and as xenografts in nude mice.
