The AACR-AstraZeneca Career Development Award for Physician-Scientists, in Honor of José Baselga has been established to honor the life and legacy of Dr. José Baselga, who was a scientific leader and supportive mentor to an entire generation of physician-scientists. The intent of this program is to encourage and support junior physician-scientists to conduct research and bolster the development of innovative targeted therapeutics.

2023 grantee

Research

Glypican 2 (GPC2) is an oncoprotein found on neuroblastoma, but not normal, tissues. The Bosse laboratory has developed human GPC2 CAR T cells that are being tested in a first-in-human Phase 1 clinical trial. In parallel, to define the role of the tumor immune microenvironment in GPC2 CAR efficacy, they developed paired-murine GPC2 CARs and performed studies in immunocompetent neuroblastoma allograft models. Results of these studies suggest that limited CAR T cell tumor trafficking and enhanced tumor infiltration of immunosuppressive myeloid-derived suppressor cells (MDSCs) may be mechanisms of GPC2 CAR immune escape. To explore these putative mechanisms further, Dr. Bosse is set to: 1) characterize how MDSCs modulate GPC2 CAR T cells, 2) develop CXCR2-armored GPC2 CARs to enhance CAR T cell tumor trafficking and circumvent MDSC-mediated immune suppression, and 3) utilize serial blood samples from their Phase 1 trial to define the relationship between MDSCs and GPC2 CAR T cell persistence and efficacy in patients with neuroblastoma.  

Biography

Dr. Bosse graduated summa cum laude with honors from Bowdoin College, and completed his medical degree and training at University of Pennsylvania and Children’s Hospital of Philadelphia (CHOP). He began studying neuroblastoma as a Howard Hughes Medical Institute Fellow during medical school. He is currently an Assistant Professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania  and CHOP.  Dr. Bosse’s laboratory at CHOP is currently focused on using an integrated genomic and functional approach to identify novel cell surface molecules for immunotherapeutic targeting in neuroblastoma and other pediatric cancers.

Acknowledgement of Support

“Receiving a 2023 AACR-AstraZeneca Career Development Award for Physician Scientists, in Honor of José Baselga, is a tremendous honor and will allow us to define mechanisms of glypican 2 CAR T cell immune escape to enable development of more potent immunotherapies for children with cancer.”

2022 Grantee

Research

Macrophages are often the predominant infiltrating immune cell in tumors, yet their potential to act as effectors of cancer immunotherapy has been underappreciated. The CD47/SIRPa interaction is a macrophage immune checkpoint, and therapies that block this interaction demonstrate the tremendous potential of macrophages to attack cancer. However, the receptors and signaling pathways that regulate macrophage activation against cancer remain poorly understood relative to other immune cell types. In this study, Dr. Weiskopf takes an unbiased approach to identify novel immune checkpoints that regulate macrophages in the tumor microenvironment. Moreover, he will employ a multi-pronged strategy to discover new small molecules and biologics that activate macrophages to attack cancer.

Biography

Kipp Weiskopf, MD, PhD earned his medical and graduate degrees at Stanford University. As a member of Irving Weissman’s laboratory, he characterized the CD47/SIRPa axis as a macrophage immune checkpoint. He previously trained at Brigham and Women’s Hospital and is board-certified in Internal Medicine. He is currently a Valhalla Fellow at Whitehead Institute for Biomedical Research, where he leads a research laboratory focused on macrophage-directed therapies for cancer. He is concurrently appointed as a medical oncology fellow at Dana-Farber Cancer Institute. He is an inventor on over 15 U.S. patents and is a cofounder of ALX Oncology.

Acknowledgment of Support

Dr. Baselga was a champion of cancer research and a fierce advocate for cancer patients. It is a tremendous honor to be supported by this award, which memorializes Dr. Baselga’s lifetime of contributions to oncology. Drawing inspiration from his example, I strive for our research to be transformative for patients.