Anti-BCMA (171) h(CD28-CD3ζ) CAR, pCDCAR1 vector

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

Details

Target
BCMA

Targeting Cell Type
T cell

Targeting Diseases
Multiple Myeloma

Generation
Second

Vector Name
pCDCAR1

Vector Length
~8kb

Vector Type
Lentiviral vector

Receptor Construction
scFv-CD28-CD3ζ

Discription of Signaling Cassetes
CD28
CD28 (Cluster of Differentiation 28) is one of the proteins expressed on T cells that provide costimulatory signals 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.
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 Retroviral transduction efficiency; cell surface staining of human T cells is consistent regardless of scFv.

CAR Construction : 171 scFv-28ζ

Fig.1 Retroviral transduction efficiency; cell surface staining of human T cells is consistent regardless of scFv.

Results from representative single donor.

Smith, E. L., Staehr, M., Masakayan, R., Tatake, I. J., Purdon, T. J., Wang, X., ... & Brentjens, R. J. (2018). Development and evaluation of an optimal human single-chain variable fragment-derived BCMA-targeted CAR T cell vector. Molecular Therapy, 26(6), 1447-1456.

Complete CAR data FuncS

Fig.2 Superior Expansion of BCMA(171) and BCMA(125) scFv Containing CAR T Cells Demonstrated by Repeat Antigen Stimulation Assay.

CAR Construction : 171 scFv-28ζ

Fig.2 Superior Expansion of BCMA(171) and BCMA(125) scFv Containing CAR T Cells Demonstrated by Repeat Antigen Stimulation Assay.

CAR T cells containing scFvs indicated (CD28 co-stimulatory domain) were placed on BCMA-aAPC or CD19-aAPC monolayers.

Complete CAR data Cyt

Fig.3 Cytotoxicity analysis; CAR+ T cells transduced with the same constructs as 1b are co-cultured at increasing E:T ratios with OPM2 human myeloma cell line.

CAR Construction : 171 scFv-28ζ

Fig.3 Cytotoxicity analysis; CAR+ T cells transduced with the same constructs as 1b are co-cultured at increasing E:T ratios with OPM2 human myeloma cell line.

All scFvs lyse OPM2 cells in a dose-dependent manner. CAR T cells incorporating scFvs 183, 171, 130, and 125 are superior to 137; mean ± SEM.

Complete CAR data FuncS

Fig.4 Treatment with BCMA(171) CAR T cells provide significantly prolonged survival compared to treatment with CD19(SJ25C1) CAR T cells.

CAR Construction : 171 scFv-28ζ

Fig.4 Treatment with BCMA(171) CAR T cells provide significantly prolonged survival compared to treatment with CD19(SJ25C1) CAR T cells.

Survival between mice treated with BCMA(171) CAR T cells differing by co-stimulatory domain were not significant.

Complete CAR data FCM

Fig.5 Generation and Validation of EGFRt/BCMA(171)-41BBz Containing CAR T Cell Therapy

CAR Construction : 171 scFv-28ζ

Fig.5 Generation and Validation of EGFRt/BCMA(171)-41BBz Containing CAR T Cell Therapy

FACS shows both the EGFRt and the CAR are co-expressed on transduced donor T cells (quadrant V++).

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.