Sarcomas are a rare group of cancers often labeled the “forgotten cancer.” Each year, between 13,000 and 16,000 people in the U.S. are diagnosed with sarcomas, and approximately 5,000 people die from these cancers annually.
Alliance for Cancer Gene Therapy (ACGT), which funds innovative research focused on the power of cell and gene therapy to transform cancer treatment, has not “forgotten” about sarcomas.
July is Sarcoma and Bone Cancer Awareness Month, and an opportunity to highlight the potential of cell and gene therapy to treat people with sarcomas. This month, ACGT is raising awareness of recent advances in cell and gene therapy research for sarcomas, the need for more progress, and how everyone can help ACGT bring new therapies to patients.
Stephen Gottschalk, MD, of St. Jude Children’s Research Hospital, is an ACGT Research Fellow focused on developing a type of cell and gene therapy called CAR T-cell therapy to treat children with sarcomas.
Dr. Gottschalk recently spoke with ACGT about the challenges of treating sarcomas, the need for new therapies, and the importance of ACGT in supporting scientists like himself with crucial funding for cutting-edge research.
After reading this Q&A, please join our mailing list for more news and updates about cell and gene therapy research advancements. Sign up here to join and receive a free monthly email newsletter along with other free communications from ACGT.
What are some of the challenges with advancing cell and gene therapies for sarcomas?
Dr. Gottschalk: “I think the biggest hurdle is the limited number of biopsy specimens and, in general, the lack of patient samples to analyze and research. For rarer cancers like sarcomas, there are just fewer patients to study whereas if you’re studying the biology of lung cancer, there are hundreds of patients.
Secondly, in a world of limited resources, more research funds are allocated to the most common cancers rather than rare cancers like sarcomas. So we need more dollars directed toward sarcoma research.”
How did you become focused on researching and studying cell and gene therapies for sarcomas?
Dr. Gottschalk: “When you look within pediatric cancer cases, we’ve made great strides in improving the survival of pediatric leukemia patients. However, there are a few cancer types, like sarcomas, where progress is lacking.
The poor outcomes of sarcomas, especially once they’ve recurred in pediatric patients, has drawn my interest to study them.”
ACGT has funded multiple research projects focused on cell and gene therapies for sarcomas. Can you explain ACGT’s impact in advancing cell and gene therapies for these cancers?
Dr. Gottschalk: “ACGT funds research that is translational. By translational, I mean taking foundational knowledge or basic science discoveries and moving them into early phase clinical testing. Unfortunately, a lot of funding organizations don’t consider this innovative enough.
On the contrary, without translational research, you’d never get these new therapies to the clinic. ACGT has done an outstanding job of funding this research phase between the basic discoveries and clinical trials. It’s this in-between phase where we roll up our sleeves and figure out whether the therapy can actually work.”
Why do sarcomas occur at a higher-than-usual rate for pediatric patients compared to other types of cancer?
Dr. Gottschalk: “Sarcomas form in bones and soft tissue – such as muscles, cartilage and fat – and often occur in areas of the body that are linked to physical growth. For example, osteosarcoma (a bone cancer) primarily occurs in the knee because the femur (bone connecting the hip and knee) has one of the longest growth spurts in the body. It’s associated with the time you grow, so that’s why sarcomas most commonly occur in children and adolescents.”
CAR T-cell therapy is approved for blood cancers such as leukemia and lymphoma. However, it has not had the same level of breakthrough for solid tumors such as sarcomas. Your ACGT-funded project is to develop a CAR T-cell therapy that targets two proteins expressed by the sarcoma cancer cells rather than just one. How does having two protein targets for CAR T cells help?
Dr. Gottschalk: “CAR T-cell therapy for leukemia and lymphoma only targets one protein: CD19. For solid tumors, there is not a single antigen (protein) expressed in these tumors at such a high level as the protein CD19 is expressed in leukemia and lymphoma. Targeting multiple antigens can give you a greater density for the CAR T cells to target. So now the T cell is able to get stimulated by two different antigens and get the same result or a better result than targeting just one antigen expressed at a very high level.
The other reason has to do with heterogeneous antigen expression. In leukemia cells, every cell expresses the target antigen at a very high level. If you look, at least right now, at the antigens we’re targeting in solid tumors, some cells express the antigens at high levels and some express the antigens at low levels. If you target two antigens, you can overcome this challenge because even if some cells express an antigen at low levels, they may express the other target antigen at a high level.
Last but not least, you can prevent immune escape. Cancer cells can evolve, and they can down-regulate (reduce or suppress) their expression of a target antigen to escape the immune system’s attack. For the cancer cell, it’s tougher to down-regulate two antigens than down-regulating just one antigen.”
Can you provide an update for your ACGT-funded research project to develop this CAR T-cell therapy for sarcomas?
Dr. Gottschalk: “We’ve moved the project into testing the therapy in animal models. We’ve been doing a lot of safety studies related to targeting this protein, and it continues to look very encouraging.
Our goal is still to move this project forward to a clinical study. Of course, there are always hurdles to overcome. Based on the data we’re generating, I’m very encouraged that these are safe targets to go after in sarcomas. The good thing about the targets is they’re not only expressed in one subtype; they are expressed in multiple types of sarcomas. This will make it much easier to run a clinical trial because we’re not going to be restricted to recruiting patients with just one type of sarcoma.”
Dr. Gottschalk’s research is funded in part by Wendy Walk and Swim Across America.
