Title: The Complete Guide to CAR-T Cells
1The Compelete Guide to
CAR-T Cells
https//www.creative-biolabs.com/car-t/
2BACKGROUND
3CAR T CELLS
PART ONE
It has a significant effect in the treatment of
acute leukemia and non Hodgkin's lymphoma, and is
considered to be one of the most promising ways
of cancer treatment. Like all technology, CAR-T
technology has experienced a long process of
evolution, and it is in this series of evolution
that CAR-T technology is becoming mature. After
treatment, the peripheral blood T cells of
patients themselves were separated, and then the
CD19-CAR molecules were expressed in high density
in T cells by retroviral vector. Such a T cell,
which expresses CD19-CAR, will identify the B
cells (normal and leukemia B cells) after being
entered in the body, and are activated to destroy
B cells by direct killing or their secreted
cytokines.
4CAR-T Treatment process
PART TWO
T cells identify tumor cells by expressing the
chimeric antigen receptor through genetic
engineering specifically. A typical CAR-T
treatment process is mainly divided into five
steps
5CAR-T Treatment process
6PART THREE
CAR Design Developemnt
T cells identify tumor cells by expressing the
chimeric antigen receptor through genetic
engineering specifically. A typical CAR-T
treatment process is mainly divided into five
steps
7CAR Design Developemnt
- The first generation of CAR mediated T cell
activation is accomplished through a tyrosine
motif on the CD3z chain or FceRIg. The CD3z chain
can provide T cell activation, cleavage of target
cells, regulation of IL-2 secretion and the
signal needed to exert anti-tumor activity in
vivo. However, the antitumor activity of the
first generation of CAR transformed T cells was
limited in vivo, and the proliferation of T cells
decreased, which ultimately led to the apoptosis
of T cells. - The second generation of CAR added a new co
stimulation signal in the cell. The experiment
proved that this made the original "signal 1"
which originated from the TCR/CD3 complex. Many
studies have shown that the second generation CAR
of "signal 2" has the same antigen specificity as
the first generation CAR with the proliferation
of T cells, the increase of cytokine secretion,
and the resistance to the secretion of cytokines.
- The secretion of apoptotic protein increased and
cell death delayed. The commonly used
costimulatory molecules are CD28, but then there
are studies to replace CD28 with CD137 (4-1BB).
In addition, the idea of using NK cell receptor
CD244 is also proposed. Compared with the first
generation of CAR, this design can increase the
memory effect on the lysis of tumor cells and the
CAR mediated killing effect.
7
8THANK YOU
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