Chimeric antigen receptor t cell therapy

1
Chimeric Antigen Receptor T Cell Therapy
Reference https//www.creative-biolabs.com/car-t/
cellrapeutics-chimeric-antigen-receptor-car-techno
logy.htm
2
Contents
01
02
CAR-T Library Technology
scFv Production in CAR Technology
04
03
Application in Animal Models
Four Generations of CARs
05
06
Bispecific CAR Construction
GMP Manufacturing and Clinical Trials
3
(No Transcript)
4
scFv Production in CAR Technology
The scFv is derived from monoclonal antibody
(mAb), which can specifically recognize the
target protein on tumor surface and subsequently
transduct activation signal into CAR-T cell. With
our one-stop solution, we can carry out scFv
generation from hybridoma cell line (full length
of monoclonal antibody) through the converting
full immune globulin (monoclonal antibodies) into
a scFv using a short flexible linker or phage
display library which has nearly 1.0 108
individual candidate clones. Furthermore,
synthesis a scFv gene based on the existed
sequence from customer is also an available
service.
5
(No Transcript)
6
CAR-T Library Technology
CAR genes with diverse antibody fragments (e.g.
scFv, Fab, VHH, scFab) against a certain target
are constructed into vectors to form the CAR-T
libraries with capacity around 108. T lymphocytes
will display these antibodies on the surface and
high-throughput screening approaches can be
performed. Due to the linkage between the T cell
activation and the expression and function of the
CARs, functional CARs are obtained with high
affinities ranging from 10 pmol to nmol. The
selected stable clones can be used in clinic
trials immediately, thus making this technology
more powerful and attractive in CAR-T cell
immunotherapy.
7
(No Transcript)
8
Four Generations of CARs

• The first generation CAR consisting of basic
  elements has been widely applied in early cancer
  immunotherapy clinical trials.
• Different from the first generation which has one
  intracellular signaling domain like CD3? or or
  FceRI?, the second-generation CAR is composed of
  an activating domain plus a co-stimulatory signal
  domain such as CD28 or 4-1BB, the structure of
  which can support longer antitumor effect.
• Similar to this strategy, two different
  co-stimulatory signaling regions are constructed
  into the third generation CARs in order to
  promote the T cell activation signal and enhance
  the proliferation and survival of CAR-T cells
  significantly.
• Furthermore, the fourth generation CAR construct
  is engineered with an inducible expression unit
  such as a cytokine (like IL-12), which can
  effectively overcome the on-target, off-tumor
  drawbacks via this inducible transgenic cytokine
  gene.

9
(No Transcript)
10
Application in Animal Models
Up to now, CAR-T cells or -NK cells have been
successfully developed and evaluated i terms of
anti-tumor effect and potential safety profile in
these animal cancer models, which can greatly
support your preclinical trial researches.
Meanwhile, these animal toxicity testing system
can also identify and assess the safety profile
of CAR modified T cells or NK cells, which
including on-target, off-tumor toxicities
targeting normal tissues and cytokine-release
syndromes.
11
(No Transcript)
12
Bispecific CAR Construction
The cocktail CAR consists of two tandem scFvs
connected by a linker, which can recognize two
different tumor antigens so as to enhance the
specificity and facilitate the activation of T
cells, especially when one cancer antigen is
downregulated or mutated. Alternatively, we can
also coexpress two distinct CAR constructs
simultaneously within T cells, such as trans-dual
specificity CAR and TanCAR. With the help of
these advanced approaches, we can greatly
increase the specificity of CAR to tumor cells
whereas decrease its toxicity to normal tissue.
13
(No Transcript)
14
Thanks
Reference https//www.creative-biolabs.com/car-t/
cellrapeutics-chimeric-antigen-receptor-car-techno
logy.htm