Anti-HIV-1 (PG9) 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
HIV-1

Targeting Cell Type
T cell

Targeting Diseases
HIV

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 co-stimulatory 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 cell 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 FuncS

Fig.1 Specific killing assay.

CAR Construction : PG9-CD3ζ

Fig.1 Specific killing assay.

Specific lysis of Cr51 labeled K562 target cells expressing HIV-1 YU2 GP160.

Leibman, R. S., Richardson, M. W., Ellebrecht, C. T., Maldini, C. R., Glover, J. A., Secreto, A. J., ... & Riley, J. L. (2017). Supraphysiologic control over HIV-1 replication mediated by CD8 T cells expressing a re-engineered CD4-based chimeric antigen receptor. PLoS pathogens, 13(10), e1006613.

Complete CAR data FCM

Fig.2 Proliferation mediated by novel CAR interactions with HIV-1-infected target cells.

CAR Construction : PG9-41BB-CD3ζ

Fig.2 Proliferation mediated by novel CAR interactions with HIV-1-infected target cells.

Primary CD8+ T lymphocytes transduced with CARs were enriched to>90% purity and labeled with CellTrace Violet and then cocultured with irradiated HIV-1 NL4-3-infected T2 cells.

Ali, A., Kitchen, S. G., Chen, I. S., Ng, H. L., Zack, J. A., & Yang, O. O. (2016). HIV-1-specific chimeric antigen receptors based on broadly neutralizing antibodies. Journal of virology, 90(15), 6999-7006.

Complete CAR data

Fig.3 Specific killing of HIV-1-infected target cells mediated by novel CARs.

CAR Construction : PG9-41BB-CD3ζ

Fig.3 Specific killing of HIV-1-infected target cells mediated by novel CARs.

CAR-transduced primary CD8+ T lymphocytes were cocultured with HIV-1-infected T2 cells in standard 4-h chromium release assays to assess killing mediated by the CARs.

Complete CAR data FuncS

Fig.4 Efficiencies of novel CAR-transduced primary CD8+ T cells against a panel of HIV-1 isolates

CAR Construction : PG9-41BB-CD3ζ

Fig.4 Efficiencies of novel CAR-transduced primary CD8+ T cells against a panel of HIV-1 isolates

CAR-transduced primary CD8+ T cells were tested against a panel of 4 subtype B viruses and one subtype C virus (TZA246) to determine the percent efficiency of log suppression

CAR scFv data SPR

Fig.5 Binding kinetics characterization.

CAR Construction :

Fig.5 Binding kinetics characterization.

Binding kinetics of PG9-iMab, iMab, and PG9 for sCD4 and monomeric gp120 (BaL strain), as determined by surface plasmon resonance.

Pace, C. S., Song, R., Ochsenbauer, C., Andrews, C. D., Franco, D., Yu, J., ... & Ho, D. D. (2013). Bispecific antibodies directed to CD4 domain 2 and HIV envelope exhibit exceptional breadth and picomolar potency against HIV-1. Proceedings of the National Academy of Sciences, 110(33), 13540-13545.

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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.