Anti-CEA (F39-11) h(CD28-OX40-CD3ζ) CAR, pSBCAR1 vector

All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.

Details

Target
CEA

Targeting Cell Type
T cell

Targeting Diseases
Pancreatic cancer

Generation
Third

Vector Name
pSBCAR1

Vector Length
~6kb

Vector Type
Sleeping Beauty (SB) transposon

Receptor Construction
scFv-CD28-OX40-CD3ζ

Discription of Signaling Cassetes
CD28
CD28 (Cluster of Differentiation 28) is one of the proteins expressed on T cells that provide co-stimulatorysignals required for T cell activation and survival. CD28 is the receptor for CD80 (B7.1) and CD86 (B7.2) proteins which are expressed on antigen-presenting cells(APC). CD28 modulates the primary TCR/CD3ζ signal in a different fashion than the late costimulatory elements OX40 and 4-1BB. CD28 enhances the expression of downstream regulators that impact on T-cell proliferation, death, differentiation, and effector functions. CAR+ T cells containing the CD28 endodomain showed strikingly enhanced sustained T cell activation, growth, survival. And CD28 results in a brightly expressed, stable receptor as the transmembrane domain. Including CD28 costimulatory domains in CARs led to enhanced anti-malignancy efficacy.
OX40
OX40, also known as CD134 or TNFRSF4 is a member of the TNFR-superfamily of receptors which is not constitutively expressed on resting naïve T cells, unlike CD28. OX40 is a secondary co-stimulatory immune checkpoint molecule, expressed after 24 to 72 hours following activation. The interaction between OX40 and its binding partner, OX40L (CD252) plays an important role in antigen-specific T-cell expansion and survival. OX40 and OX40L also regulate cytokine production from T cells and modulate cytokine receptor signaling. OX40 cosignaling in CAR improve redirected T-cell effector functions and enhance anti-tumor activity.
CD3ζ
CD3ζ, also known as T-cell receptor zeta, which together with T-cell receptor and CD3γ, δ , ε chain, forms the TCR-CD3 complex. ζ was expressed independently from the complex. The zeta chain plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways. CD3-zeta,which contains 3 ITAMs, is the most commonly used endodomain component of CARs. It transmits an activation signal to the T cell after antigen is bound. CD3-zeta may not provide a fully competent activation signal and additional co-stimulatory signaling is needed. For example, chimeric CD28 and OX40 can be used with CD3-zeta to transmit a proliferative/survival signal, or all three can be used together.

Target

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Published Data

Complete CAR data FCM

Fig.1 Phenotypic analysis of CEA-specific CAR-T cells. CEA-specific CARs on mouse T cells transduced using retroviral vectors were analyzed after staining with biotinylated-CEA followed by staining with anti-CD4C, CD8C, CD62L, and CD127.

CAR Construction : F39-11 scFv-28ζ

Both CD4C and CD8C T cells expressed CAR that could bind CEA on the cell surfaces.

Wang, L., Ma, N., Okamoto, S., Amaishi, Y., Sato, E., Seo, N., ... & Shiku, H. (2016). Efficient tumor regression by adoptively transferred CEA-specific CAR-T cells associated with symptoms of mild cytokine release syndrome. Oncoimmunology, 5(9), e1211218.

Complete CAR data Cyt

Fig.2 Cytotoxic activity of CEA-specific CAR-T cells against CEA (MC38) and CEAC (MC32a) gastric tumor cell lines in 6-h 51Cr-release assays.

CAR Construction : F39-11 scFv-28ζ

Fig.2 Cytotoxic activity of CEA-specific CAR-T cells against CEA (MC38) and CEAC (MC32a) gastric tumor cell lines in 6-h 51Cr-release assays.

The marginal, if any, antitumor effect of CAR-T cells seen in mice that did not receive preconditioning was closely associated with rapid disappearance of transferred CAR-T cells in the peripheral blood.

Complete CAR data FuncS

Fig.3 Tumor growth curves of mice transferred with CAR-T cells.

CAR Construction : F39-11 scFv-28ζ

Fig.3 Tumor growth curves of mice transferred with CAR-T cells.

WT and CEA-Tg mice bearing 7-d-old MC38 or MC32a tumors were transferred with CEA-specific CAR-T cells. Some mice also received lymphodepleting preconditioning as indicated. Tumor volumes were measured by a calliper using the formula (length x width) at the indicated time points (n=5).

Complete CAR data IHC

Fig.4 Severe weight loss and the eventual death of CEA-Tg mice transferred with CEA-specific CAR-T cells.

CAR Construction : F39-11 scFv-28ζ

Fig.4 Severe weight loss and the eventual death of CEA-Tg mice transferred with CEA-specific CAR-T cells.

Cryostat sections of organs collected from mice at 17 day after tumor inoculation were subjected to CD45.1 immunohistochemistry.

More Published Data More Published Data

For research use only. Not intended for any clinical use. No products from Creative Biolabs may be resold, modified for resale or used to manufacture commercial products without prior written approval from Creative Biolabs.

Anti-CEA (F39-11) h(CD28-OX40-CD3ζ) CAR, pSBCAR1 (CAR-SB-02LX361)

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