Abramson Cancer Center, University of Pennsylvania
Where CAR-T became a drug (June, Levine; Emily Whitehead), mRNA was made druggable (Karikó, Weissman), and PARP PET was invented.
CTL019/tisagenlecleucel, mRNA modification (Nobel 2023), in vivo CAR-T origins (Capstan), 18F-FluorThanatrace PARP PET, proton therapy, Basser Center for BRCA.
- CAR-T and in vivo CAR
- mRNA
- PARP PET
- BRCA (Basser Center)
Angela DeMichele led the first palbociclib clinical trial and co-leads the I-SPY 2 adaptive platform.
Built the manufacturing that turned CAR-T from a lab idea into a product given to thousands of patients.
Developed the CD19 CAR-T therapy that became the first approved gene-modified cell therapy for cancer.
Showed that adding blood-based sequencing to tissue testing finds more targetable lung cancer mutations.
Treated the first adult CLL patients with CAR-T and reported a decade of durable remissions.
Drew Weissman is the Nobel laureate whose modified-mRNA discovery underlies mRNA vaccines and now in vivo CAR-T.
The first child treated with CAR-T cells, in 2012. Her recovery from relapsed leukaemia turned an experimental idea into an approved therapy.
Lynn Schuchter is a melanoma oncologist who led ASCO in 2023-24.
Mitchell Schnall is the radiologist who brought imaging research into the ECOG-ACRIN cooperative group.
Peter O'Dwyer is a GI oncologist who co-leads ECOG-ACRIN, one of the NCI's national trial networks.
Robert Mach invented the PARP PET tracer FluorThanatrace that images DNA repair capacity in tumours.
Directs Penn's cancer centre and pioneered CD40 agonist immunotherapy for pancreatic cancer.
Leads the world's first centre dedicated to BRCA-related cancers and the trials of PARP inhibitors plus immunotherapy.
JULIET, with ZUMA-1, showed that CAR-T could rescue a substantial minority of adults with chemotherapy-refractory lymphoma and that complete responders often stay in remission. The lower toxicity of a 4-1BB construct and the option of bridging therapy made it usable in a broader population. The high drop-out between enrolment and infusion remains a lesson about turnaround time.
ELIANA turned CAR-T from a single-centre experiment into a licensed product and created the regulatory and logistical template every later cell therapy has followed. For children with refractory leukaemia it offers a chance of durable remission without transplant. The trial also exposed the gaps: manufacturing failures, patients dying while waiting, and roughly half relapsing within a few years.
This paper is the proof-of-concept for a living drug: a single infusion of a patient's own engineered T cells could eradicate leukaemia that had survived chemotherapy, transplant and antibody therapy. It defined cytokine release syndrome and its antidote, tocilizumab, and revealed antigen-loss relapse. It led directly to the first approved gene-modified cell therapy three years later.
For women who carry a BRCA mutation, preventive removal of the ovaries and tubes saves lives, and preventive mastectomy almost eliminates breast cancer. These are the strongest prevention effects in oncology, which is why finding carriers before they develop cancer matters so much.