What is an Antibody Drug Conjugate?
- There is a relatively new kind of cancer therapy available called antibody drug conjugates, and this new therapy is “incredibly promising,” one expert says.
- This new therapy is also proving itself effective in treating advanced-stage bladder cancer.
- Antibody drug conjugates are a type of immunotherapy for cancer. This medicine targets bladder cancer cells that express the protein nectin-4, which is present in most bladder cancers.
Dr. Debasish Sundi, a urological oncologist at the Ohio State University Comprehensive Cancer Center in Columbus, tells SurvivorNet that antibody drug conjugates are a type of immunotherapy for cancer. “The reason for that is (because) a really essential part of this type of treatment is an antibody,” he says. This medicine targets bladder cancer cells that express the protein nectin-4, which is present in most bladder cancers.Read More
Checkpoint inhibitors are man-made antibodies that shut down key proteins on immune cells like PD-L1 — essentially halting a cancer’s ability to spread. These drugs have been proven effective for treating certain later-stage cancers.
With this knowledge in mind, Dr. Sundi says, “if you now think of what an antibody drug conjugate is, it’s a little bit of a different type of immunotherapy.” Here’s what you need to know:
What is an Antibody Drug Conjugate?
Dr. Sundi explains that with an antibody drug conjugate, “there’s an antibody that’s designed to recognize a specific cancer-related protein. And we call it an antibody drug conjugate because the antibody is kind of used as a homing missile, if you will, against the cancer cell, and is conjugated (hence the name) or connected to another medicine.”
This is like the payload that actually kills the cancer cells, he says.
Antibody drug conjugates are composed of three different components: a monoclonal antibody (mAb) and a cytotoxic payload made from a chemotherapy agent, which are connected together using a chemical linker.
Dr. Sundi says that a great example of an antibody drug conjugate for advanced-stage bladder cancer is enfortumab vedotin (brand name: PADCEV). The drug is an antibody connected to a chemotherapy drug. It basically blocks cell division, he explains, “it is a microtubules inhibitor, and in so doing, it kills cancer cells and that’s how a lot of chemo therapies work.”
“But what’s really neat here is because the chemotherapy is connected to this antibody or conjugated to this antibody, if the antibody can recognize cancer cells, then this medicine, at least in theory, will deliver the chemotherapy in a very specific manner directly to the cancer cell,” Dr. Sundi says.
If you recall earlier, it was said that an antibody drug conjugate targets bladder cancer cells that express the protein nectin-4. This is a molecule that promotes cell growth, Dr. Sundi says, and it also happens to be really highly expressed in bladder cancer. “We think over 80 percent of bladder cancers have a lot of this molecule, nectin-4.”
Antibody Drug Conjugate FDA Approvals
As you can see, this relatively new therapy is proving itself to be incredibly promising. So, you may be wondering why more doctors aren’t talking about it.
One reason for this, some have expressed, could be that there are 10 antibody drug conjugates available and approved by the U.S. Food and Drug Administration — all but one in the last 10 years, and all but three since 2017, “the promise of this modality is now bearing fruit,” reports Pharmaceutical Technology, an online media outlet covering pharmaceuticals. But Dr. Sundi thinks that these drug approvals are actually a major achievement, as the process of oncology drug approval from the FDA standpoint is “incredibly rigorous.”
“If you look at approvals for antibody drug conjugates, or many cancer types compared to what’s happening for bladder cancer, over the past six years that looks a little anemic,” Dr. Sundi says. “But actually, three FDA-approved antibody drug conjugates is, I think, huge progress for a relatively new class of drugs.”
For nearly three decades, Dr. Sundi says, there were no new FDA approvals for patients with advanced bladder cancer; all that was available was cisplatin chemotherapy. (Cisplatin chemotherapy was approved in 1978 for testicular cancer and is now the standard-of-care for treating advanced-stage bladder cancer.)
“Several decades passed, and we had nothing. And that’s maybe an extreme example, but an FDA-approved new medicine for an aggressive cancer type is a big deal,” Dr. Sundi says. “It doesn’t happen all the time.”
“This is really kind of like a fire hydrant, and at full blast, as far as approvals go,” he adds. “This is not common, this is reason to celebrate. (There are now) so many new effective options for patients.”