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Hello my name is Joseph Fraietta and
I'm an assistant professor in the Department of Microbiology,
Director of the Solid Tumor Immunotherapy Laboratory in the Center for Cellular Immunotherapies
and a member of the standing faculty of the Abromson Cancer Center
at the University of Pennsylvania.
It's a great pleasure to speak to you about
Chimeric Antigen Receptor, CAR, T cell therapies for cancer.
I'll begin with the history of immunotherapy which is
an old field with a long and checkered history.
It started in the 1890s when a young physician named William Coley observed that a patient with
cancer who survived a severe bacterial infection also cleared their cancer.
Over the next 100 years, several strategies have been tried,
mostly revolving around vaccines and cytokines to
overcome T cell tolerance.
It wasn't until about 2010,
when T cell therapy for prostate cancer was approved
and checkpoint blockade with ipilimumab for melanoma showed a survival benefit,
that there was a real resurgence of interest in immunotherapy for cancer.
Checkpoint blockade also with PD-1 and PD-L1 is incredibly promising
active in multiple tumor types as published in
four seminal New England Journal of Medicine papers over the span of two years.
In that timespan, CAR modified T cells also showed durable remissions
in acute lymphoblastic leukemia and chronic lymphocytic leukemia,
and that's when immunotherapy really took off.
The successes of several CAR T cell clinical trials paved
the way for five United States Food and Drug Administration, or FDA,
approved CAR T cell therapies, three of which have
also gained European Medicines Agency, or EMA, approval.
Four of these therapies target the CD19 protein,
a B cell lineage marker that's present both on malignant and healthy B cells.
These therapies are approved for the treatment of
relapsed refractory B cell acute lymphoblastic leukemia, diffuse large B cell lymphoma,
mantle cell lymphoma and/or large B cell lymphomas.
Recently the first CAR T cell therapy to target
B cell maturation antigen, or BCMA, for patients with
multiple myeloma who progressed or do not respond to at least four prior lines of conventional therapy,
was FDA approved.
This indicates is that CAR T cells appear to be entering the mainstream of immuno-oncology.
Why did it take 100 years?