Anti-LAG3 (TSR-033) 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
LAG3

Targeting Cell Type
T cell

Targeting Diseases
infectious diseases

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

CAR scFv data FCM

Fig.1 Simultaneous blockade of LAG-3 and PD-1 synergizes to elicit increased efficacy, immune stimulation, and immunologic memory in mouse A20 lymphoma
model.

CAR Construction :

Fig.1 Simultaneous blockade of LAG-3 and PD-1 synergizes to elicit increased efficacy, immune stimulation, and immunologic memory in mouse A20 lymphoma model.

Mice (n =4 per group) were sacrificed on day 36, and pharmacodynamic changes in immune cells in the spleen were assessed.

Ghosh, S., Sharma, G., Travers, J., Kumar, S., Choi, J., Jun, H. T., ... & Jenkins, D. (2019). TSR-033, a Novel Therapeutic Antibody Targeting LAG-3, Enhances T-Cell Function and the Activity of PD-1 Blockade In Vitro and In VivoAnti-LAG-3 Synergy with PD-1 Blockade in Mouse Tumor Models. Molecular cancer therapeutics, 18(3), 632-641.

CAR scFv data ELISA

Fig.2 TSR-033 binds LAG-3 on resting CD4 and CD8 T cells in health human donors.

CAR Construction :

Fig.2 TSR-033 binds LAG-3 on resting CD4 and CD8 T cells in health human donors.

Total LAG-3 was detected using a noncompeting anti human LAG-3 antibody.

CAR scFv data Inhibit

Fig.3 TSR-033 inhibits binding of labeled LAG-3 Fc fusion protein to MHC Class II expressing Daudi cells.

CAR Construction :

Fig.3 TSR-033 inhibits binding of labeled LAG-3 Fc fusion protein to MHC Class II expressing Daudi cells.

Data are representative of at least two separate occasions.

CAR scFv data FuncS

Fig.4 TSR-033 amplifies T-cell effector function, particularly in combination with anti-PD-1.

CAR Construction :

Fig.4 TSR-033 amplifies T-cell effector function, particularly in combination with anti-PD-1.

The functional activity of TSR-033 was evaluated in an MLR assay, in which primary human CD4 T cells were mixed with monocyte-derived dendritic cells from a different donor.

CAR scFv data FCM

Fig.5 FACS staining of Lag3 and CD3 expression for Jurkat Cell.

CAR Construction :

Fig.5 FACS staining of Lag3 and CD3 expression for Jurkat Cell.

All measurements were performed in triplicate.

Bhagwat, B., Cherwinski, H., Sathe, M., Seghezzi, W., McClanahan, T. K., de Waal Malefyt, R., & Willingham, A. (2018). Establishment of engineered cell-based assays mediating LAG3 and PD1 immune suppression enables potency measurement of blocking antibodies and assessment of signal transduction. Journal of immunological methods, 456, 7-14.

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.

pCDCAR1 LAG3 h(28ζ) (CAR-ZP3551)

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