Anti-CD38 (056) h(41BB-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
CD38

Targeting Cell Type
T cell

Targeting Diseases
Multiple myeloma

Generation
Second

Vector Name
pCDCAR1

Vector Length
~8kb

Vector Type
Retroviral

Receptor Construction
scFv-41BB-CD3ζ

Discription of Signaling Cassetes
41BB
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 antigen-nonspecific 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 Efficacy of CD38-CART cells at lysing MM cell lines.

CAR Construction : 056-41BB-CD3ζ

Fig.1 Efficacy of CD38-CART cells at lysing MM cell lines.

In 24 h cytotoxicity assays, three different types of CD38-CART cells were tested against two MM cell lines with different CD38 expression levels: (Upper) U266, a CD38− cell line, (Bottom) UM9, a CD38+ cell line.

Drent, E., Groen, R. W., Noort, W. A., Themeli, M., van Bueren, J. J. L., Parren, P. W., ... & Mutis, T. (2016). Pre-clinical evaluation of CD38 chimeric antigen receptor engineered T cells for the treatment of multiple myeloma. Haematologica, 101(5), 616.

Complete CAR data FCM

Fig.2 Efficacy of CD38-CART cells generated from healthy individuals at lysing primary MM cells.

CAR Construction : 056-41BB-CD3ζ

Fig.2 Efficacy of CD38-CART cells generated from healthy individuals at lysing primary MM cells.

Bone marrow-derived mononuclear cells from three MM patients and bone marrow mononuclear cells from two AML patients were co-incubated with no, mock- or CD38-CART cells generated from healthy peripheral blood mononuclear cells for 16 h.

Complete CAR data FCM

Fig.3 CART cell phenotyping assay.

CAR Construction : 056-41BB-CD3ζ

Fig.3 CART cell phenotyping assay.

Analysis of CD38-CART cells after 2 weeks of in vitro culture, with fluorescence-labeled mono -clonal antibodies for CD45RA and CD62L and CD38.

Complete CAR data BI

Fig.4 In vivo efficacy of CD38-CAR-T cells against multiple myeloma tumors growing in a humanized microenvironment.

CAR Construction : 056-41BB-CD3ζ

Fig.4 In vivo efficacy of CD38-CAR-T cells against multiple myeloma tumors growing in a humanized microenvironment.

Mice were implanted with fully humanized bone marrow stromal cell scaffolds each coated with 1×106 UM9-GFP-Luc tumor cells. At 7, 9 and 13 days after implantation, mice were injected intravenously with 20×10^6 mock or CD38-CART cells.

CAR scFv data FCM

Fig.5 Apparent affinity of selected CD38 antibodies.

CAR Construction :

Fig.5 Apparent affinity of selected CD38 antibodies.

Indicated values are the apparent affinities (ug/ml) determined by flow cytometry binding to target cell lines CHO-CD38 and Daudi.

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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.