Expert Discusses Promise of Novel Sarcoma Vaccine and Other Ongoing Research in the Field

Seth M. Pollack, MD

Seth M. Pollack, MD

Seth M. Pollack, MD, has one of the only labs in the United States that is focused primarily on immunotherapy treatments for various types of sarcoma. Most recently, his lab has been working with Immune Design on clinical trials for a sarcoma vaccine, CMB305, which is targeted at the NY-ESO-1 protein.

His group’s research also focuses on investigating the microenvironments of different sarcoma subtypes to better understand how immune cells attract inside the tumor. These findings have become useful when studying potential immunotherapy treatments for specific sarcoma subtypes, Pollack says.

In an interview withTargeted Oncology, Pollack, assistant member, Clinical Research Division, assistant professor, Division of Oncology, University of Washington, and attending physician at Seattle Cancer Care Alliance, discussed some of the advancements his lab is making in the field of sarcoma.

TARGETED ONCOLOGY: Can you share some of the research you are working on in your lab?

Pollack:My lab focuses on immunotherapy for sarcoma, and we got started by being very focused on NY-ESO-1. NY-ESO-1 is a protein made by certain types of synovial sarcoma. One of the earlier discoveries our lab made was that another type of sarcoma called myxoid/round cell liposarcoma almost always expresses this protein as well. This protein is a really good target for immunotherapy. It’s been known for a long time to be expressed by a small percentage of many different kinds of cancers, but in these 2 sarcomas, it’s expressed almost always. When it’s expressed, it’s expressed really strongly throughout the whole tumor. From our studies, we were able to develop ways to isolate T cells to target the NY-ESO-1 from the blood of these patients.

We have a trial where we treated patients with these T cells, and we found that even though some of these patients had their tumors shrink, they didn’t shrink completely or in a way that was durable. This led us to study what was happening inside the tumor in the microenvironments, to try and understand how immune cells in the tumor attract. We looked at a number of different sarcoma types for this and we found that certain sarcomas have very inflammatory microenvironments, for example, undifferentiated pleomorphic sarcomas have relatively inflamed microenvironments, where certain sarcomas have a type of very quiet microenvironment, like synovial sarcoma and myxoid/round cell liposarcoma. That’s sort of the basis for a lot of what we are doing now.

TARGETED ONCOLOGY: Can you discuss the sarcoma vaccine you are currently working on?

Pollack:The vaccine is made by a company called Immune Design. It’s the first-ever vaccine for cancer that’s made from a lentivirus. Lentivirus is a special kind of virus that is a live virus vaccine, engineered so that it only affects the dendritic cells, which are the cells that tell the rest of the immune system where to go. This isn’t my trial, but we have been very involved in it. We’ve helped design the trial and participated in moderating in my lab so it helps Immune Design figure out whether the patients’ T cells were actually responding to NY-ESO-1.

In the first trial of this vaccine, it definitely seemed that most of the patients had responses against NY-ESO-1 after treatments. In particular, there was one patient that had nearly a complete response, over 85% tumor reduction that’s continuing over 3 years after she had the vaccine. That’s not the typical response, but that is what is possible with the vaccine. This vaccine is getting ready to be in a phase III trial that’s going to be nationwide and including Europe and Asia. That is something we are really excited about.

Through our work characterizing the tumor microenvironment, we also realized that tumor-associated macrophages seem to be very important parts of the cancer’s resistance to immune responses. Because of that, we designed a number of trials to both kill the tumor-associated macrophages to cause immunogenic cell death in the tumor that would not be too toxic for the T cells and then co-administer a checkpoint inhibitor to try and increase the T-cell response at the same time we are doing all of this. We have 1 trial going on of pembrolizumab (Keytruda) that we are very excited about. Another trial we are very excited about is combining a drug called trabectedin (Yondelis) for patients with liposarcoma and leiomyosarcoma.

TARGETED ONCOLOGY: What areas of research are you particularly excited about in the field of sarcoma?

Pollack:Ithink in cancer in general, everyone is very excited about cellular therapies, T cells that are genetically modified to attack the cancer. Everyone is particularly excited about the success that centers like ours and others have had in treating acute lymphoblastic leukemia using this approach. There’s been some success using NY-ESO-1 targeted T-cell receptors to fight synovial sarcoma and myxoid/round cell liposarcoma. There’s a company called Adaptive that’s interested in making T-cell receptors to do this. We got a grant from the Alliance for Cancer Gene Therapy to further develop NY-ESO-1 targeted T cells using both CD8 and CD4 for NY-ESO-1 specific T cells. That’s another thing we are really excited about.

TARGETED ONCOLOGY: You have been working to increase the number of sarcoma cancer samples in the tissue bank. How is this database being used?

Pollack:We work closely with the Northwest Sarcoma Foundation to do this, and they have been a great supporter. The Northwest Sarcoma Foundation is a community organization that does a lot of patient outreach and gives a lot of grants to patients for travel back and forth for doctor appointments and things.

Through their support, as well as other support, we started a tissue bank which now has over 1000 samples and some of the work I’ve already told you about—such as characterizing the microenvironment—is coming out of our work with tissue banking and having samples from bank specimens. I think that’s really important, and that’s how the next generation of trials gets made, by setting these specimen that we already have.

TARGETED ONCOLOGY: What are some challenges that exist within the field of sarcoma that still need to be addressed?

Pollack:One of the biggest problems with sarcoma is that sarcoma is rare, but it’s not that rare. It is only 1% of cancers, but so many people get cancer that when you start looking around, you’re surprised by how many patients do have these rare diseases. What is also true is that there is a lot of different types of sarcoma, and some of the subtypes really are truly rare. Studying some of these rare types is going to be the challenge.

We are getting better at studying some of the more common subtypes. For example,leiomyosarcoma has a lot of work to do, but I think people are recognizing the importance of leiomyosarcoma. Over 2000 people a year get leiomyosarcoma. It’s similar for undifferentiated pleomorphic sarcoma and liposarcoma. However, some of the sarcoma subtypes, for example, hemangiosarcoma is a pretty rare subtype, and it is hard to make significant progress in this subtype without the patient numbers to run clinical trials focused on that subtype.