The Complete Guide to CAR-T Therapy

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The Complete Guide to CAR-T Therapy
www.creative-biolabs.com/car-t
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Part 1
Chimeric Antigen Receptor T Cell
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The chimeric antigen receptor (CAR), a major
component of CAR-T, confers T-cell independent
ability to recognize tumor antigens in an
HLA-dependent manner, allowing CAR-engineered T
cells to recognize broader targets compared to
native T cell surface receptors. The basic design
of CAR includes a tumor-associated antigen (TAA)
binding region (usually derived from scFV
segments of the monoclonal antibody
antigen-binding region), an extracellular hinge
region, a transmembrane region and an
intracellular signal Area. The choice of the
target antigen is a key determinant of the
specificity and availability of CAR and the
safety of the genetically modified T cells
themselves.
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The ideal target antigen is a tumor-specific
antigen expressed on the surface of tumor cells
alone. Unfortunately, most antigens expressed by
tumors do not have tumor-specific features, so
most CARs target tumor-associated antigens, which
often leads to off-target chances. At the same
time, the relevant antigen selection also needs
to be careful to avoid selecting secreted
antigens in order to avoid the possibility of
CAR-T off target.
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Part 2
Common Targets
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As for commonly used targets at this stage, in
addition to CD19, ERRB2 (HER-2 / neu) is also a
target to treat lung and prostate cancer,
targeting prostate-specific antigen treatment of
prostate cancer, targeting CAIX treatment of
renal cell carcinoma, targeting Lewis Y to treat
lung cancer and ovarian cancer and so on, which
clearly shows that CAR-T cells are widely used in
anti-tumor applications. It is worth to mention
that, at 2015 annual meeting of the American
Society of Oncology, there is a report that
researchers at the University of Pennsylvania
have used the mesothelin as a target to construct
CAR T successfully for the treatment of
pancreatic cancer. 6 patients involved were
effectively treated, which shows CAR-T in solid
tumors also has a promising future.
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Part 3
CAR T development
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The first generation of CAR-mediated T-cell
activation is accomplished via the
tyrosine-activated motif on the CD3z chain or
FceRIg. The CD3z chain can provide the signals
required for T cell activation, lysis of target
cells, regulation of IL-2 secretion, and in vivo
antitumor activity. However, the antitumor
activity of the first generation of
CAR-transformed T cells is limited in vivo, and
the decrease of T cell proliferation eventually
leads to T cell apoptosis. The second generation
of CAR adds a new costimulatory signal
intracellularly.
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Creative Biolabs
Designing a chemically compatible antibody for
the conjugation chemistry is a key step that
directly dictates the fate of an ADC project.
With expertise and dedication, advanced antibody
design platform and services from Creative
Biolabs will be your best companion in creating
customized ADCs. Please contact us for more
information and a detailed quote.
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Contact us
45-1 Ramsey Road, Shirley, NY 11967, USA
Email marketing_at_creative-biolabs.com
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