Anti-CD19 (CTL019) 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
CD19

Targeting Cell Type
T cell

Targeting Diseases
Chronic lymphocytic leukemia

Generation
Second

Vector Name
pCDCAR1

Vector Length
~8kb

Vector Type
Lentiviral

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 FuncS

$Fig.1 Clinical Responses to CTL019 Infusion in Two Children with Relapsed, ChemotherapyRefractory Acute Lymphoblastic Leukemia (ALL).$

CAR Construction : CTL019 scfv-CD28-CD3ζ

Fig.1 Clinical Responses to CTL019 Infusion in Two Children with Relapsed, ChemotherapyRefractory Acute Lymphoblastic Leukemia (ALL).

Figure shows serum levels of cytokines and inflammatory markers measured at the indicated time points after CTL019 infusion. Cytokine values are shown with the use of a semilogarithmic plot indicating change from baseline.

Ruella, M., Xu, J., Barrett, D. M., Fraietta, J. A., Reich, T. J., Ambrose, D. E., ... & Melenhorst, J. J. (2018). Induction of resistance to chimeric antigen receptor T cell therapy by transduction of a single leukemic B cell. Nature medicine, 24(10), 1499-1503.

Complete CAR data FuncS

$Fig.2 Clinical Responses to CTL019 Infusion in Two Children with Relapsed, ChemotherapyRefractory Acute Lymphoblastic Leukemia (ALL).$

CAR Construction : CTL019 scfv-CD28-CD3ζ

Fig.2 Clinical Responses to CTL019 Infusion in Two Children with Relapsed, ChemotherapyRefractory Acute Lymphoblastic Leukemia (ALL).

Figure shows changes in the circulating absolute neutrophil count (ANC), absolute lymphocyte count (ALC), and white-cell count. The increase in the ALC was primarily from activated CTL019 T lymphocytes.

Grupp, S. A., Kalos, M., Barrett, D., Aplenc, R., Porter, D. L., Rheingold, S. R., ... & June, C. H. (2013). Chimeric antigen receptor–modified T cells for acute lymphoid leukemia. New England Journal of Medicine, 368(16), 1509-1518.

Complete CAR data FuncS

Fig.3 Expansion and Visualization of CTL019 Cells in Peripheral Blood, Bone Marrow, and Cerebrospinal Fluid (CSF).

CAR Construction : CTL019 scfv-CD28-CD3ζ

Fig.3 Expansion and Visualization of CTL019 Cells in Peripheral Blood, Bone Marrow, and Cerebrospinal Fluid (CSF).

Figure shows the results of flow-cytometric analysis of peripheral blood stained with antibodies to detect CD3 and the anti-CD19 chimeric antigen receptor. Depicted is the percentage of CD3 cells expressing the chimeric antigen receptor in Patients 1 and 2.

Complete CAR data FuncS

Fig.4 Expansion and Visualization of CTL019 Cells in Peripheral Blood, Bone Marrow, and Cerebrospinal Fluid (CSF).

CAR Construction : CTL019 scfv-CD28-CD3ζ

Fig.4 Expansion and Visualization of CTL019 Cells in Peripheral Blood, Bone Marrow, and Cerebrospinal Fluid (CSF).

Figure shows the presence of CTL019 T cells in peripheral blood, bone marrow, and CSF as assessed by means of a quantitative real-time polymerase-chain-reaction (PCR) assay.

Complete CAR data FuncS

Fig.5 Expansion and Visualization of CTL019 Cells in Cerebrospinal Fluid (CSF).

CAR Construction : CTL019 scfv-CD28-CD3ζ

Fig.5 Expansion and Visualization of CTL019 Cells in Cerebrospinal Fluid (CSF).

Figure shows flow-cytometric detection of CTL019 cells in CSF from Patients 1 and 2.

Complete CAR data FuncS

Fig.6 Expansion and Visualization of CTL019 Cells in Cerebrospinal Fluid (CSF).

CAR Construction : CTL019 scfv-CD28-CD3ζ

Fig.6 Expansion and Visualization of CTL019 Cells in Cerebrospinal Fluid (CSF).

Figure shows activated large granular lymphocytes in Wright-stained smears of the peripheral blood and cytospin preparations of
CSF from Patient 2.

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.