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CTLA-4 Gene Editing    

CTLA-4 or TLA4 (cytotoxic T lymphocyte-associated protein 4), also known as CD152 (differentiation cluster 152), is the second receptor for members of the B7 family. CTLA-4 is an important negative regulator of T cell-mediated immune responses. It is constitutively expressed in regulatory T cells (Treg) but can only be expressed after activation in conventional T cells. Treg and memory T cells have an intracellular pool of CTLA-4 cells that are used to recover endosomes that can rapidly circulate to the cell surface upon activation. CTLA-4 plays a key role in maintaining immune homeostasis and is a checkpoint to limit immune response.

CTLA-4 acts as a checkpoint or "brake" when activating T cells through a variety of overlapping mechanisms. First, CTLA-4 competes with CD28 for binding to its ligands B7-1 and B7-2, and the binding of CTLA-4 to B7 helps prevent T cells from killing other cells, including cancer cells. Second, CTLA-4 involvement triggers intracellular changes that inhibit T cell activation. Proposed mechanisms for inhibition of signaling include (1) association with intracellular phosphatases, such as phosphatase 1 (SHP-1), SHP-2 and protein phosphatase 2A (PP2A) containing the Src homology 2 (SH2) domain, (2) Blocking lipid raft expression, and (3) disrupting the formation of microclusters. Finally, CTLA-4 sends a suppression signal to APC via B7.

Since the CTLA-4 pathway is thought to regulate the activation of T cells in naive early proliferating T cells, mainly in lymph nodes. Thus, blockade of CTLA-4 can induce an anti-tumor immune response by promoting activation and proliferation of tumor-specific T cells (Figure 1).

 The prevailing view: CTLA-4 checkpoint blockade results in tumor immunityFigure 1: The prevailing view: CTLA-4 checkpoint blockade results in tumor immunity (Fei Tan. 2018).

CTLA-4 Gene Editing Service

CRISPR/Cas9 PlatformCB, as a leading biological commercial company, offers expert services for our clients including human disease models in vivo or in vitro. One of our mission is to provide high-quality services to our partners in the research of the CRISPR system. In order to improve the gene-editing speed of candidates, we provide custom CRISPR/Cas9 gene-editing services to help you effectively control target genes deleted, inserted or point mutated in cells or animals. And our staff will work with you to fit your research needs.

  • CTLA-4 Gene Editing Cell Line Generation

We have successfully implemented CTLA-4 CRISPR/Cas9 gene edited in both easy-to-transfect cell lines and hard-to-transfect cells. To support your projects, we will offer you full-length custom CTLA-4 gene editing service from strategy design to final stable cells. Our CTLA-4 gene editing cell line generation services include:

➢ gRNA design and synthesis
➢ Transfect the cell lines you're interested
➢ Select the high expression cells and sort monoclonal cell
➢ Validate the knockout/knock-in/point mutation of CTLA-4 by PCR and sequencing
➢ Produce cryogenic preserved vials of stable cells and a final report

Host cell lines available: HEK239T, Hela, HepG2, U87, Ba/F3, CHO, MDA-MB-453, MDA-MB-231NIH3T3, T47D, Neuro2a, MCF7, RKO, K562, RAW264.7, etc.

  • CTLA-4 Gene Editing Animal Model Generation

CRISPR/Cas9 PlatformCB also has extensive experience in incorporating CRISPR-Cas9 technology into animal models, which have been fully recognized by our clients. Tell us your needs, we provide an end-to-end CTLA-4 CRISPR/Cas9 gene-editing animal service and guarantee at least 2 founders or 3 F1 animals with shorter turnaround time and lower price. Our CTLA-4 gene editing animal model generation services include:

➢ CTLA-4 gene conventional knockout animals
➢ CTLA-4 gene conditional knockout animals
➢ CTLA-4 point mutation animals
➢ CTLA-4 knockin animals

Alternative species: mouse, rat, rabbit, zebrafish, C. elegans, etc.

CRISPR/Cas9 PlatformCB is a leading biotech company specializing in offering a set of services for gene editing in cells and animals. Our high-quality data and efficiency of the experimental cycle meet the demands from the early gRNA design to the final cell lines and animals, acquiring the customer's consistent good comments. There is no doubt that CRISPR/Cas9 PlatformCB will be your best partner to support your research.

Related Products at CRISPR/Cas9 PlatformCB

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CSC-RT2373Human CTLA4 Knockout Cell Line-HelaInquiry

References

  1. Intlekofer AM & Thompson CB. At the bench: preclinical rationale for CTLA-4 and PD-1 blockade as cancer immunotherapy. J Leukoc Biol. 2013; 94(1):25-39.
  2. Gardner D. et al. Understanding the CD28/CTLA-4 (CD152) pathway and its implications for costimulatory blockade. Am J Transplant. 2014; 14(9):1985-1991.
  3. Buchbinder EI. et al. CTLA-4 and PD-1 pathways: similarities, differences, and implications of their inhibition. Am J Clin Oncol. 2016; 39:98-106.
  4. Bernice Lo & Ussama M Abdel-Motal. Lessons from CTLA-4 deficiency and checkpoint inhibition. Current Opinion in Immunology. 2017; 49:14–19.
  5. Lucy S.K. Walker & David M. Sansom. Confusing signals: Recent progress in CTLA-4 biology. Trends Immunol. 2015; 36(2):63–70.
  6. Fei Tang. et al. Anti-CTLA-4 antibodies in cancer immunotherapy: selective depletion of intratumoral regulatory T cells or checkpoint blockade? Cell Biosci. 2018; 8:30.
For research use only. Not intended for any clinical use.
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