Anti-CD4 (Ibalizumab) h(4-1BB-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
CD4

Targeting Cell Type
T Cell

Targeting Diseases
Breast cancer

Generation
Second

Vector Name
pCDCAR1

Vector Length
~8kb

Vector Type
Lentiviral vector

Receptor Construction
scFv-4-1BB-CD3ζ

Discription of Signaling Cassetes
4-1BB
CD137 (also known as 4-1BB) is a surface co-stimulatory glycoprotein originally described as present on activated T lymphocytes, which belongs to the tumor necrosis factor (TNF) receptor superfamily. It is expressed mainly on activated CD4+ and CD8+ T cells, and binds to a high-affinity ligand (4-1BBL) expressed on several antigen-presenting cells such as macrophages and activated B cells. On the basis of preclinical observation, this molecule can promote the persistence of antigen-specific and antigennonspecific chimeric antigen receptor T-cells to significantly increases antitumor 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 The immunophenotype of CD4CAR T cells.

CAR Construction : Ibalizumab-CD28-41BB-CD3ζ

Fig.1 The immunophenotype of CD4CAR T cells.

The immunophenotype of CD4CAR T cells was evaluated at the end of each culture.

Pinz, K., Liu, H., Golightly, M., Jares, A., Lan, F., Zieve, G. W., ... & Ma, Y. (2016). Preclinical targeting of human T-cell malignancies using CD4-specific chimeric antigen receptor (CAR)-engineered T cells. Leukemia, 30(3), 701-707.

Complete CAR data FCM

Fig.2 CD4CAR T cells derived from PBMCs specifically kill CD4-expressing the tumor cell line.

CAR Construction : Ibalizumab-CD28-41BB-CD3ζ

Fig.2 CD4CAR T cells derived from PBMCs specifically kill CD4-expressing the tumor cell line.

KARPAS 299 cells incubated with CD4CAR T cells overnight were eliminated at a rate of 38%, 62%, and 85%, at E:T ratios of 2:1, 5:1, and 10:1

Complete CAR data FuncS

Fig.3 The anti-tumor activity of CD4CAR T cells in vivo.

CAR Construction : Ibalizumab-CD28-41BB-CD3ζ

Fig.3 The anti-tumor activity of CD4CAR T cells in vivo.

Treatment with CD4CAR T cells significantly prolonged the survival of mice bearing KARPAS 299 lymphoma as compared to treatment with the GFP-transduced control T cells.

Complete CAR data FuncS

Fig.4 AAV-CD4CAR induces antitumor activity in vitro.

CAR Construction : Ibalizumab-CD28-41BB-CD3ζ

Fig.4 AAV-CD4CAR induces antitumor activity in vitro.

48 hours after co-culture with AAV-CD4CAR T cells, MT2, and Jurkat cells were effectively lysed in a dose-dependent manner. However, neither the CD4- cell line (H929) nor the MT2 cells treated with a CD20-CAR were lysed.

Nawaz, W., Huang, B., Xu, S., Li, Y., Zhu, L., Yiqiao, H., ... & Wu, X. (2021). AAV-mediated in vivo CAR gene therapy for targeting human T-cell leukemia. Blood cancer journal, 11(6), 1-12.

Complete CAR data FACS

Fig.5 Cytokine production in an ATL NCG-HuPBL mouse model.

CAR Construction : Ibalizumab-CD28-41BB-CD3ζ

Fig.5 Cytokine production in an ATL NCG-HuPBL mouse model.

Graphical representation of different cytokines detected in the plasma of tumor-bearing ATL NCG-HuPBL mice.

Nawaz, W., Huang, B., Xu, S., Li, Y., Zhu, L., Yiqiao, H., ... & Wu, X. (2021). AAV-mediated in vivo CAR gene therapy for targeting human T-cell leukemia. Blood cancer journal, 11(6), 1-12.

Complete CAR data BI

Fig.6 In vivo-generated AAV-CD4CAR T cells mediated antitumor activity.

CAR Construction : Ibalizumab-CD28-41BB-CD3ζ

Fig.6 In vivo-generated AAV-CD4CAR T cells mediated antitumor activity.

In vivo imaging of luciferase-expressing MT2 ATL cells injected into NCG-HuPBL mice after AAV or PBS (untreated) injection.

Nawaz, W., Huang, B., Xu, S., Li, Y., Zhu, L., Yiqiao, H., ... & Wu, X. (2021). AAV-mediated in vivo CAR gene therapy for targeting human T-cell leukemia. Blood cancer journal, 11(6), 1-12.

Complete CAR data BI

Fig.7 Anti-leukemic effects of CD4CAR NK cells in vivo.

CAR Construction : Ibalizumab-CD28-41BB-CD3ζ

Fig.7 Anti-leukemic effects of CD4CAR NK cells in vivo.

NSG mice bearing luciferase-expressing KARPAS-299 cells were treated with CD4CAR NK cells or vector control NK cells.

Pinz, K. G., Yakaboski, E., Jares, A., Liu, H., Firor, A. E., Chen, K. H., ... & Ma, Y. (2017). Targeting T-cell malignancies using anti-CD4 CAR NK-92 cells. Oncotarget, 8(68), 112783.

CAR scFv data SPR

Fig.8 Affinity determination of ibalizumab.

CAR Construction :

Fig.8 Affinity determination of ibalizumab.

Binding affinity of ibalizumab to hCD4 as assessed in a Biacore assay.

Song, R., Franco, D., Kao, C. Y., Yu, F., Huang, Y., & Ho, D. D. (2010). Epitope mapping of ibalizumab, a humanized anti-CD4 monoclonal antibody with anti-HIV-1 activity in infected patients. Journal of virology, 84(14), 6935-6942.

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