I have researched and written about ADC's (glembatumumab vedotin in particular) before. Here are a couple of posts: Antibody-Drug Conjugate for melanoma
In 2013 I wrote:
"An ADC (antibody drug conjugate) is like a Trojan Horse!!! It takes a bad ass cytotoxin, like auristatin (that's the one being used here), an anti-mitotic agent that derives its action by preventing tubulin polymerization and therefore stops cell division, attaches it via a special molecule to a monoclonal antibody that targets antigens preferentially expressed on the surface of the targeted cancer cells..in this case, Endothelin B. This method allows patients to survive being treated with really toxic agents without suffering the terrible side effects that would certainly ensue should those cytotoxins be injected directly. By taking them under cover, only the bad cells we want to target are damaged."
"ADC's have been in the works since the 80's. Over that time laboratory researchers have found many more possible antibodies to use (and studied which tumors express them the most) and a variety of gradually improving techniques to "link" the chemotherapeutic agent to the antibody. Improved "linkers" seem to have made it easier to use a variety of antibodies as well as cytotoxic agents while keeping the whole little trifecta intact until it reaches its destination. Patent information seems to indicate that researchers feel they may even be able to target infectious organisms in the future. Two ADC's have been marketed for lymphoma and leukemia. And, just a couple of weeks ago, Celldex got FDA approval for CDX-011 (glembatumumab vedotin) as a treatment for Her-2 breast cancer. Interestingly, initially, this drug which uses "auristatin conjugated to a monoclonal antibody that recognizes GPNMB, expressed at higher levels in melanoma and breast tumors" was tested in patients with melanoma as well as breast cancer. Sievers and Senter, in a Seattle Genentech report state, "In a phase I/II trial in patients with unresectable late-stage melanoma, CDX-011 showed overall response rates ranging from 14% to 19% depending on dosing frequency and GPNMB expression levels." However, at this point, it seems that this particular ADC is no longer being utilized in melanoma trials."
Now there is this...looking at CDX011-05 ~
Not sure about the future of this therapy. They really need to work on making the "link" stronger so that there is less leakage of the chemo that leads to much of the side effects. Perhaps that is what they tried to do in the CDX011-05 version...don't know. Also not sure about a decreased ORR in this study compared to the previous. However, I will be forever grateful to this therapy for keeping one of my dearest ones around for a year more, giving him time to find a therapy that worked better for him in the end.
This one's for my dear J and F!!!! love, c