Immunotherapy, Canine Patients, & Genomic Instability: 2023 Grant Recipients

This year, the Osteosarcoma Institute awarded over $1.7 million across four innovative osteosarcoma research projects.

This year, the Osteosarcoma Institute (OSI) awarded over $1.7 million in osteosarcoma research funding to four national and international grant recipients through its 2023-2024 grant cycle. After a rigorous review of 24 submissions, the OSI’s expert review committee selected four innovative osteosarcoma research projects. These proposals demonstrated rigorous science and the potential to push osteosarcoma treatment forward.

“Some studies we fund are called high-risk studies because they may not get past the first year if the theory does not work,” says Lee Helman, MD, the OSI’s director and an expert in the field of osteosarcoma. “We need breakthroughs to move the field forward. We need to do something different than we have been doing for the last 30 years.”

The Frontline spoke with Dr. Helman to learn about each of this year’s funded cancer research projects.

Searching for Immunotherapy for Osteosarcoma

Scientists have not yet uncovered a successful immunotherapy for osteosarcoma. Two of this year’s selected grants aim to develop better immunotherapy options for osteosarcoma patients.

Seth M. Pollack, MD

Optimizing B7-H3 CAR T Cells for Osteosarcoma: $500,000

This study, led by Seth M. Pollack, MD, of Northwestern University Feinberg School of Medicine, examines immunotherapy in canine patients. The study will supplement CAR-T cell therapy with additional agents that modify the tumor environment to make the CAR-T cell therapy more effective. For example, researchers will use gamma interferon (a signaling chemical that is part of the body’s adaptive immunity) to augment the immune system. Because osteosarcoma in dogs is strikingly similar to osteosarcoma in humans, the hope is that improving treatment for canine osteosarcoma will also yield insights that can one day translate into human patients. “I think it is a fantastic opportunity and, hopefully, it will inform our next studies in trying to use CAR-T cell therapy in human patients,” says Dr. Helman.

Poul Sorensen, MD, PhD

Harnessing the Osteosarcoma Surfaceome for Immunotherapy Targets to Block Metastatic Capacity: $500,000

The second immunotherapy study is led by Poul Sorensen, MD, PhD. This study aims to identify new proteins that are unique to the surface of metastatic osteosarcoma cells and so can serve as immunotherapy targets. Once the team identifies possible targets, the next step will be to develop antibody-drug conjugates or CAR-T cells that can selectively block those proteins and test whether the treatment is successful in reducing tumor growth.

Understanding Osteosarcoma’s Genomic Instability

The other two studies are centered on better understanding osteosarcoma’s profound genomic instability. Osteosarcoma tumors are constantly evolving, and the structure and number of their chromosomes is extremely abnormal.

Isidro Cortés-Ciriano, PhD

Decoding the Role of Chromothripsis on the Clonal Evolution and Chemoresistance of Osteosarcomas: $499,914

Isidro Cortés-Ciriano, PhD, of the Hinxton, United Kingdom, location of the European Molecular Biology Laboratory, leads one of the genomic studies. Dr. Cortés-Ciriano is studying the causes and consequences of osteosarcoma’s complex genome disarray. Using clinical tumor samples and a novel data analysis framework based on evolutionary biology, his team will work to identify the proteins involved in these complex aberrations that can then be targeted through immunotherapy or targeted therapy.

“We need breakthroughs to move the field forward. We need to do something different than we have been doing for the last 30 years.” — Lee Helman, MD, Director of the Osteosarcoma Institute

Evolutionary Dynamics and Drivers of Osteosarcoma: $220,000

Christina Curtis, PhD, MSc, of Stanford University, will also explore the causes and effects of osteosarcoma’s genomic instability. Her study will use artificial intelligence to better understand cancer genomics. In a process called longitudinal sampling, Dr. Curtis will analyze how the same tumor evolves into multiple branches over time using sophisticated technology including RNA sequencing and spatial genomics. “If we could understand how a cell can tolerate these weird cell divisions that lead to this scrambled genome, and if we could learn how osteosarcoma evolves, we might be able to find osteosarcoma’s Achilles’ heel,” says Dr. Helman.

Christina Curtis, PhD, MSc (front row center in blue) and her lab at Stanford Medicine

The Grant Process

The OSI is a leading funder of osteosarcoma research, including clinical trials, correlative science, and preclinical/translational studies. The best way to apply for funding is through the two-stage annual grant cycle, which opens in September with Letters of Intent due in mid-November. For the 2023-2024 grant process, the OSI has added a High-Risk/High-Impact pilot program to fund bold new ideas that may fall within any part of a drug development path, and that seek to deliver curative outcomes to patients with osteosarcoma. If you are a patient, family, or foundation interested in co-funding research with the OSI, please email giving@osinst.org.