The Role of Immunotherapy in Carcinosarcoma
An interview with Dr. Michael Birrer
1. Diane Redington: What is the role of emerging immunotherapies relative to this research and potential therapies down the road?
Answer, Dr. Michael Birrer: As you know, immunotherapy is a hot topic and has shown some spectacular responses in other tumors. The early data for ovarian cancer has not been overwhelming. But again, I think a lot of that is not applicable to carcinosarcoma because it’s a different tumor. And there is some early molecular data to suggest that the targets for immunotherapy, like PD-L1 and PD-1, are present in the tumor. So I think it is a good candidate. And there’s the type of trial where you really want to do it and do it right, you need to have multiple centers across the US dedicated to carcinosarcoma and a well-written trial that is open at all those sites.
2. Diane Redington: How do we make that happen?
Answer, Dr. Michael Birrer: Well, it takes motivated investigators, which I think we are. It takes a network of dedicated clinician researchers, which I think we have. Certainly, I know the sites throughout the United States who would be willing to do this. And then finally, as you know, what drives everything is financial resources. Now, if we could get a pharmaceutical company interested, then that would be the ideal source. The complaint usually is that it’s a small market and we have bigger things to do. But that can be addressed. If the science behind it is really strong, you can get companies interested.
3. Diane Redington: What about the immunotherapies like the vaccine trials? Does that have any relevance here? Or the antibody drug conjugate therapies?
Answer, Dr. Michael Birrer: I am most enthusiastic about the immunotherapy trials using the immune checkpoint inhibitors [PD-L1], which I just discussed. I think vaccines are more problematic for a couple of reasons. First of all, I don’t think the targets for the vaccines have been well characterized. Some of the work we are doing may be able to do that. What you are looking for are proteins that come from the genes that have been mutated – they’ve been changed. They make good vaccine targets. So we need to do some work on that. The second concern about vaccines is I think most of us believe that they are helpful in very small volume disease. They kind of clean up. They mop up what is left. So for recurrent tumors, they would be a little more challenging. But certainly still a worthy area of research.
And then there is Adoptive T-cell experiments. These are the CAR T-cells [Chimeric Antigen Receptor T-cell]. That’s a really exciting area. Led to some spectacular responses in ALL [acute lymphoblastic leukemia], for instance.
4. Diane Redington: Is that where you are creating the antigen using the tumor to create an antigen?
Answer, Dr. Michael Birrer: That would be autologous T-cell transfer where you’re priming the T-cell – the patient’s own T-cells – and then putting them back in. CAR T-cells are actually engineered T-cells. They are being engineered to a protein that’s on the surface of the tumor. And that’s where the challenge is. We need to find those for carcinosarcoma.
Diane Redington: Well, you better get busy!
Dr. Michael Birrer: You notice the common theme, which is – a lot of this in the clinic leads back to getting the science right, which is why this project is so important. Because it should deliver a lot of those endpoints. Cell surface markers, mutational peptides. These are all important things to lead to clinical trials.
Diane Redington: Well, again, I can’t thank you enough. I feel so fortunate that we were able to connect and establish this wonderful research and meet your team. You guys inspire me every day. I just can’t thank you enough.
Dr. Michael Birrer: You inspire us. That’s why we do it. Thank you.