Although companies, investors and academics are all
racing to develop chimeric antigen receptor-based T cells for cancer, numerous
basic science questions still surround the technology. The way forward will
likely involve combining chimeric antigen receptors with antibodies, ligands or
other small molecules to add specificity and safety to current therapies.
Eye on the
T cells are engineered to express either a CAR or TCR that interacts with a
tumor-associated antigen (see "Receptor
expression and engagement of antigen"). The T cells become activated when they
encounter antigen-expressing tumor cells. The result is elimination of the
malignant cells and expansion and proliferation of the T cells to provide
A moving target
T cell therapeutics may themselves induce changes in a
tumor by applying selective pressure that facilitates downregulation of the
target cancer antigen or causes proliferation of tumor cells that lack the
target cancer antigen. In some cases, these changes result from altered
conditions in the tumor microenvironment.
opinion leaders who attended the summit said that
combinatorial strategies provide the best option so far for controlling T cell
activity and suggested that T cells should be designed to interact with two
antigens instead of one.
to Seth Ettenberg, head of oncology biologics at the Novartis Institutes for BioMedical Research, no single model
exists to reveal everything that needs to be known about toxicity or durable
responses to therapy.
As more information is being uncovered about how T cells
interact with the tumor microenvironment, it is becoming clear that initial T
cell success can be dampened as tumor microenvironment conditions change during
the course of treatment.
Make it work
As the scientific issues are being sorted out,
manufacturing and clinical protocol issues also require attention.
addition, the panel recommended further exploration of allogeneic cells as a
platform for making CAR- or TCR-based T cell therapies more readily available
as off-the-shelf solutions.
as scientific and clinical progress continue, it still remains murky who owns
the IP to the various components or procedures needed to create engineered,
CAR-based T cells.
Baas, T. SciBX 7(25);
doi:10.1038/scibx.2014.725Published online June 26, 2014
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AND INSTITUTIONS MENTIONED
University of Pennsylvania, Philadelphia, Pa.
Atlas Venture, Cambridge, Mass.
Baylor College of Medicine, Houston, Texas
Bellicum Pharmaceuticals Inc., Houston, Texas
bluebird bio Inc.
(NASDAQ:BLUE), Cambridge, Mass.
Celgene Corp. (NASDAQ:CELG),
Cellectis S.A. (Euronext:ALCLS),
The Children's Hospital of Philadelphia, Philadelphia, Pa.
Dendreon Corp. (NASDAQ:DNDN), Seattle, Wash.
Fred Hutchinson Cancer Research Center, Seattle, Wash.
GlaxoSmithKline plc (LSE:GSK; NYSE:GSK), London, U.K.
Juno Therapeutics Inc., Seattle, Wash.
Kite Pharma Inc.
(NASDAQ:KITE), Los Angeles, Calif.
Memorial Sloan-Kettering Cancer Center, New York, N.Y.
National Cancer Institute, Bethesda, Md.
National University of Singapore, Singapore
Novartis AG (NYSE:NVS; SIX:NOVN),
Novartis Institutes for BioMedical Research, Cambridge, Mass.
OrbiMed Advisors LLC, New York, N.Y.
Perelman School of Medicine at the University of
(NYSE:PFE), New York, N.Y.
Seattle Children's Hospital, Seattle, Wash.
St. Jude Children's Research Hospital, Memphis, Tenn.
University of Pennsylvania, Philadelphia, Pa.
University of Washington, Seattle, Wash.