UCSF is at the forefront of the worldwide effort to harness the potential of cellular therapies for cancer treatment. Our physicians and scientists lead innovative laboratory and clinical research to provide first-in-class treatments to our patients. Much of this work, funded by philanthropy, is taking the field in new directions, including treatments for rare cancers.
A recent $1 million gift has helped establish the UCSF Sarcoma Cellular Therapy Initiative led by Kole Roybal, PhD, director of the UCSF Parker Institute for Cancer Immunotherapy, and Brian Schulte, MD, medical director of the UCSF Sarcoma Program. Below, Roybal and Schulte discuss the vision for the new initiative and the power of visionary philanthropy in creating breakthroughs.
Q. Your team recently received a $1 million gift from a donor to develop the UCSF Sarcoma Cellular Therapy Initiative. Please talk about your vision around innovating new treatments for sarcoma/osteosarcoma and the need for better therapies for this rare
Schulte: Sarcoma is a collection of rare neoplastic diseases which are mesenchymal in origin, meaning from progenitor cells that form structural elements of the body like bone, muscle, and fat. There are over a hundred types of sarcoma. The UCSF Sarcoma Cellular Therapy Initiative will allow us to focus and leverage the distinct capabilities of UCSF, namely our unparalleled expertise in clinical management of sarcoma, basic science research, and cellular therapies to answer important questions, and ultimately create potent therapies for these rare cancers. Osteosarcoma disproportionately affects young people, or adolescents and young adults. Utilizing some of its unique properties, we believe we can create unique therapies that will benefit our patients with advanced disease. What’s so incredible about UCSF is that we have all the resources we need available on one campus. There’s nowhere better in the world to start this project.
Roybal: Osteosarcoma has a high probability of relapse, and there is a lack of innovative therapies that can safely eliminate the more aggressive and resistant recurrent tumor. Our vision is to engineer T cell therapies that can directly address the recurrent tumors that are difficult to treat. The $1 million gift will be used to develop an engineered T cell therapy that incorporates a unique set of technologies developed at UCSF that enhance the T cell’s ability to eliminate relapsed osteosarcoma safely and durably. The initial research will provide the pre-clinical data to initiate a clinical trial to test the safety and efficacy of the next-generation T cell therapy in collaboration with Dr. Schulte.
Q. Who are the primary members of this team and what is each person’s expertise and contribution?
Schulte: As the medical director of the UCSF Sarcoma Program, I am intimately involved in the clinical management of our patients with sarcoma. I help direct the medical side of therapy for patients and integrate our care with other specialists. Likewise, in my role within the sarcoma program, I co-chair our site committee and have experience in composing, reviewing, and running research protocols as an investigator.
Roybal: As the UCSF director of the Parker Institute for Cancer Immunotherapy and an associate professor in the Department of Immunology my research group works at the forefront of engineered immune cell therapies for cancer. Our interdisciplinary research has led to the clinical development of next-generation engineered immune cell therapies capable of precise, controlled, and customizable therapeutic activity in tumors.
Gregory Allen, MD, PhD: Dr. Allen is a translational medical oncologist who has been able to bridge the gap between the bench and the bedside. His work has been transformational around cellular therapeutics, uncovering new and novel methods of treatment for cancers previously thought to be 'immunologically cold' such as pancreatic cancer. He is going to be an incredible asset in building therapies for patients with osteosarcoma and other sarcomas.
Rosie Wustrack, MD: Dr. Wustrack has tremendous experience in the surgical management of sarcoma and has expertise in creation of various models, in vitro and in vivo or sarcoma. She brings with her decades of practical knowledge and involvement in building and growing our understanding of local and systemic therapies for sarcomas. It's no surprise that with her amazing track record she has become the acting chair of the department of orthopedic surgery.
Q. This initiative will be another element in UCSF’s established and burgeoning efforts to harness the potential of cellular therapies for cancer treatment. How will our collaboration-rich environment benefit this initiative and vice versa?
Schulte: UCSF is a rich nexus of research for cellular therapies. The last few months have been incredibly eye opening. Along the way, I have met so many thoughtful, warm, and insightful colleagues who are beyond motivated to make a difference for our patients with sarcoma. It is very much our expectation that by advancing our understanding and therapeutic approaches for sarcomas, we will be able to learn lessons that apply readily to other cancers and projects at UCSF. It is my perspective that focusing on sarcoma, given its diversity, is going to likely dovetail with other groups in a profound way. There is a tremendous ability to make a difference, and quickly.
Roybal: Few major breakthroughs in science or therapeutic development occur in isolation. We have assembled a team that has the combined expertise to execute on the development of a next-generation cell therapy for osteosarcoma. We have the clinical insight to inform how we engineer the T cell therapy (Schulte and Wustrack). We also have unique homegrown UCSF technologies to engineer T cell therapies (Roybal and Allen) that are capable of precisely and effectively eliminating tumors that are resistant to all current therapeutic modalities. Our team’s combined expertise plus the burgeoning infrastructure to manufacture and administer next-generation cell therapies at UCSF (The Living Therapeutics Initiative) will help us to reach the lofty yet achievable goals of this osteosarcoma initiative.
Q. What do you hope to achieve over the next five years?
Schulte: I suppose that I’ve been called an optimist frequently when it comes to my expectations for the field of oncology, and in particular sarcoma. My honest expectation is that within five years we will be moving forward into early phase clinical trials for patients with osteosarcoma and eventually other subtypes. There’s certainly a lot of work to be done between now and then, but with the excitement and capability of our team here, what might be bullish at other institutions becomes sensible.
Roybal: We seek to develop a transformative engineered T cell therapy that successfully eliminates recurrent osteosarcoma. To accomplish this, we will engineer T cells that 1) precisely recognize osteosarcoma with novel receptor technologies developed in the Roybal lab and; 2) have multiple enhancements developed in the Roybal lab and Allen lab that improve T cell activity in resistant tumors and stimulate broad tumor immunity that can drive long-term durable remission.
Q. Given how intensely competitive it can be to obtain funding, especially for rare cancers, please talk about the impact donors have? What will this gift enable you to do?
Schulte: Philanthropic donations can be the lifeblood of projects for rare diseases. As mentioned, other typical mechanisms of funding may not be as available. These gifts can serve as a catalyst and drive further growth and impact. That is what we’re seeing here. This donation has allowed us to build momentum for the Sarcoma Cellular Therapies Initiative, enabling us to hire scientists, conduct in vitro and in vivo assays and construct something that will eventually be used clinically. It is vital for getting started on this work and it cannot be overstated how important it and future philanthropy will be as our projects progress.
Roybal: Brian covered much of my thoughts. I would add that philanthropic funds that are provided quickly and without major constraints can catalyze rapid development of therapeutics. This potentially accelerates the timeline for treating patients with rare cancers such as osteosarcoma by a year to two years when compared to the traditional grant process.
Thus, the benefits are two-fold – we can develop therapies that are bold and transformative instead of incremental, and the path to clinical implementation where true impact for patients is realized can be expedited.