While chimeric antigen receptor T-cell (CAR-T) therapy does not have much to do with pediatric gastroenterology, the development of this therapy, described recently (L Rosenbaum NEJM 2017; 377: 1313-5), holds lessons about perseverance and chance that are widely applicable.
CAR-T involves genetically engineering the patient’s own T cells to kill tumor cells. It recently received FDA approval to treat patients up to 25 years of age with relapsed or refractory acute lymphoblastic leukemia.
The story of the survival of Emily Whitehead, the index patient for this therapy, is suitable for Hollywood. The groundwork for this very expensive treatment dates back to 1893 with William Coley’s recognition of the immune system’s potential for treating cancer –he injected streptococcus into an inoperable osteosarcoma and observed tumor shrinkage.
Key Steps in this Story:
- University of Pennsylvania’s immunologist Carl June spent his career working on CAR-T. His wife died of ovarian cancer in 2001 and he resolved to develop this emerging immunotherapy that he had wanted for her.
- Barbara and Edward Netter provided key funding for this project in 2008. They too had lost a close family member to cancer.
- Emily Whitehead nearly died due to CAR-T therapy which triggered cytokine-release syndrome, which was not a recognized entity at the time. In part due to chance, extremely high levels (>1000-fold) of interleukin-6 (IL-6) were detected quickly due to the ability of the institution and prodding by the researchers to their colleagues. This allowed the experimental use of tocilizumab, a monoclonal antibody that targets IL-6.
- Her survival helped reenergize this line of research.
My take (borrowed from author): “Therapeutic advances are motivated by more than money –that it’s the hope, vision, and perseverance of both patients and investigators that made this …possible.”
Acute esophageal necrosis ina a 63 year-old that resolved with conservative treatment. “The cause is unknown..[it] occurs most commonly in the distal third of the esophagus, which is hypovascular” often in the setting of chronic disease.
gutsandgrowth 