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CD19

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  • Background
  • Anti-CD19 CAR-T Services
  • Anti-CD19 CAR-T In Vitro Assay Services
  • Anti-CD19 CAR-T In Vivo Assay Services
  • Product List

Background

CD19 (Cluster of Differentiation 19), also called B lymphocyte antigen CD19, is a protein that in human is encoded by CD19 gene. The human CD19 antigen is a 95 kd transmembrane glycoprotein. It is found on the surface of B cell, function as B cell co-receptor that assemble with B cell antigen receptor in order to decrease the threshold for antigen receptor dependent stimulation. CD19 is usually expressed on follicular dendritic cells and B cells. As a hallmark of B cell, CD19 has highly conserved expression on most B cell tumors, though there is no strong evidence to show if CD19 contributes to B cell carcinogenesis directly. It is expressed in most acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and B cell lymphomas. In fact, the majority of B cell malignancies express CD19 at normal to high levels (80% of ALL, 88% of B cell lymphomas, and 100% of B cell leukemias). For these reasons, CD19 is also a potential target for lymphoma therapy. Several monoclonal antibodies and other antibody-based immune therapy such as CAR-T technique are targeted at CD19. It is foreseeable that CD19 mAb and molecularly engineered chimeric antigen receptor will be widely studied for therapies of lymphoma, leukemia, and autoimmune disorders.

Fig.1 CD19 molecular structure. (Wang, Guoqing & Delong, 2012)

Fig.1 Structure of CD19 molecular.1

Associated Disease

Anti-CD19 CAR-T Services

  • CD19 CAR-T In Vitro Assays

CD19 CAR-T Expression Test

Creative Biolabs offers a complete series of CD19 protein products including biotinylated CD19, unconjugated CD19, and fluorescent-labeled CD19, which can efficiently identify the expression of anti-CD19 CAR on the surface of the transduced T cells and have been broadly employed for the quality control release testing and pharmacokinetic (PK) research of anti-CD19 CAR-T cells.

Schematic of LbCpf1 mRNA electroporation combined with AAV-delivered crRNA and HDR template (AAV-Cpf1).

Fig.2 Sensitivity of the detection reagents to detect CD19-specific CAR-T cells in PBMCs (Schanda, et al., 2020). The figure shows CD19-specific CAR-T cells that were serially diluted in PBMCs of the same healthy donors at six different dilutions.

CD19 CAR-T Cytokine Release Test

The synchronous activation of CAR T cells encountering CD19-expressing leukemic cells and B lymphocytes directly results in cytokine release syndrome (CRS). Creative Biolabs provides unique cytokine release tests. For example, enzyme-linked immunosorbent assay (ELISA) to detect the secretion of Interferon gamma (IFNγ), Interleukin-2 (IL-2), and other cytokines.

Fig.3 Cytokine secretion in CD19 CAR-T cells enhanced by TERT mRNA delivery. (Bai, et al., 2015)

Fig.3 Cytokine release of TERT mRNA delivery to CD19 CAR-modified T cells.3 Four groups of T cells—GFP-T, CAR-T, CI-CAR-T, and TERT-CAR-T—were co-cultured with CD19+ Raji cells at varying E:T ratios. TERT mRNA-transduced CD19 CAR T cells exhibited cytokine secretion levels similar to those observed in the control groups

CD19 CAR-T In Vitro Cytotoxicity Assay

Anti-CD19 CAR-T lymphocytes therapy shows excellent effects in patients with B lymphocyte neoplasias, which can induce remission in young adults and children with lymphoid leukemia. Creative Biolabs offers proprietary cytotoxicity test for CD19 CAR-T cells. In CD19 CAR-T cells, the cytotoxic activity can be evaluated by luciferase assay and by lactate dehydrogenase (LDH) assay.

Targeting cell type of CD19 at Creative Biolabs includes:

T cell
NK cell

Schematic of LbCpf1 mRNA electroporation combined with AAV-delivered crRNA and HDR template (AAV-Cpf1).

Fig.4 Cytotoxicity in CD19 CAR-T cells (An, et al., 2016). The cytolytic activity was measured by assays of lactate dehydrogenase (LDH) release after coculturing using the detection kit.

CD19 CAR-T Cell Proliferation Test

For evaluating our CAR products, Creative Biolabs has complete CAR testing services including cell proliferation tests to make sure the CAR-modified immune cells can be activated effectively once they encounter the target cells. The activation and proliferation process of CD19 CAR T cells can be measured via CFSE in vitro.

Schematic of LbCpf1 mRNA electroporation combined with AAV-delivered crRNA and HDR template (AAV-Cpf1).

Fig.5 CD19 CAR-T cell proliferation (Castella, et al., 2018). A) Total cell number at different time points. B) Percentage of CAR19-expressing cells at different time points.

  • CD19 CAR-T in vivo Assays

CD19 CAR-T Cell Therapy Animal Models

Creative Biolabs has established comprehensive efficacy models to facilitate in vivo efficacy evaluation including immune-oncology animal models, syngeneic models, humanized mice models, patient-derived xenografted (PDX) models, patient-derived organoid models, and cell line derived xenografted (CDX) models, such as raji xenograft model and MCL xenograft model for CD19 CAR-T therapy.

The human tumor cell lines of CDX models provided for CD19 CAR-T cell therapy at Creative Biolabs include:

NAML6 cell line
Raji cell line
MCL cell line

Fig.6 Anti-CD19 CAR-T cell humanized mouse models. (Mhaidly & Els, 2020)

Fig.6 In vivo CAR T cell generation in humanized mice.6

Efficacy Test of CD19 CAR-T

Therapeutic efficacy test of CD19 CAR-T cells in animal models provides valuable information for later clinical application. Creative Biolabs is able to conduct many techniques to evaluate the therapeutic efficacy of the CD19 CAR-T cell therapy including bioluminescence imaging (BLI), survival curve analysis, and FACS analysis of PBMC.

Schematic of LbCpf1 mRNA electroporation combined with AAV-delivered crRNA and HDR template (AAV-Cpf1).

Fig.7 in vivo evaluation of CD19 CAR-T efficacy (Castella, et al., 2018). A) A timeline of experimental design. B) Bioluminescence images showing disease progression on different days.

Toxicity Evaluation CD19 CAR-T

With extensive experience in preclinical in vivo research and project management, Creative Biolabs provides comprehensive CD19 CAR-T cell toxicity evaluation services with appropriate models. The toxicological study services include clinical observation, cytokine release analysis, tumor lysis analysis, tumorigenicity study, and so on.

Please feel free to contact us for more CD19 CAR-T in vivo assays.

References

  1. Wang, Kemeng, Guoqing Wei, and Delong Liu. "CD19: a biomarker for B cell development, lymphoma diagnosis and therapy." Experimental hematology & oncology 1 (2012): 1-7.
  2. Schanda, Nicola, et al. "Sensitivity and specificity of CD19. CAR-T cell detection by flow cytometry and PCR." Cells 10.11 (2021): 3208.
  3. Bai, Yun, et al. "Enhancement of the in vivo persistence and antitumor efficacy of CD19 chimeric antigen receptor T cells through the delivery of modified TERT mRNA." Cell Discovery 1.1 (2015): 1-15.
  4. An, Na, et al. "Construction of a new anti-CD19 chimeric antigen receptor and the anti-leukemia function study of the transduced T cells." Oncotarget 7.9 (2016): 10638.
  5. Castella, Maria, et al. "Development of a novel anti-CD19 chimeric antigen receptor: a paradigm for an affordable CAR T cell production at academic institutions." Molecular Therapy-Methods & Clinical Development 12 (2019): 134-144.
  6. Mhaidly, Rana, and Els Verhoeyen. "Humanized mice are precious tools for preclinical evaluation of CAR T and CAR NK cell therapies." Cancers 12.7 (2020): 1915.
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Product List

To support the development of CD19-targeted antibody-based CAR-T therapy, Creative Biolabs has developed a comprehensive series of CD19 molecular-related products, such as CAR vector products, CAR cell products, CAR viral particles, CAR animal cells, and so on. Please browse the list below to find the right product for you.

  • CAR Vector Products

  • TCR Vector Products

  • AbTCR Vector Products

  • TCR Cell Products

  • CAR Cell Products

  • CAR Viral Particles

  • Protein

  • TriCAR Vector Products

  • TCR-Like CAR

  • CAR-MA Vector Products

  • CAR-MA Cell Products

  • CAR Animal Cells

  • CAR mRNA

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  • Target Species:
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CAT Product Name Target Species Antibody Clone Antibody Host Receptor Construction Vector Type Targeting Cell Type CAR Vector Type Inquiry & Datasheet
CAR-YF001 Anti-CD19 (FMC635-H4) h(4-1BB-CD3ζ) CAR, pCDCAR1 Human FMC635-H4 Mouse scFv-4-1BB-CD3ζ Lentiviral vector T cell   Add to Cart   Datasheet
CAR-YF002 Anti-CD19 (FMC635-H4) h(CD28-CD3ζ) CAR, pCDCAR1 Human FMC635-H4 Mouse scFv-CD28-CD3ζ Lentiviral vector T cell   Add to Cart   Datasheet
CAR-YF019 Anti-CD19 (CBL-YF002) h(4-1BB-CD3ζ) CAR, pCDCAR1 Human CBL-YF002 Mouse scFv-4-1BB-CD3ζ Lentiviral vector T cell   Add to Cart   Datasheet
CAR-YF020 Anti-CD19 (CBL-YF002) h(CD28-CD3ζ) CAR, pCDCAR1 Human CBL-YF002 Mouse scFv-CD28-CD3ζ Lentiviral vector T cell   Add to Cart   Datasheet
CAR-YF025 Anti-CD19 (CBL-YF005) h(4-1BB-CD3ζ) CAR, pCDCAR1 Human CBL-YF005 Humanized scFv-4-1BB-CD3ζ Lentiviral vector T cell   Add to Cart   Datasheet
CAR-YF026 Anti-CD19 (CBL-YF005) h(CD28-CD3ζ) CAR, pCDCAR1 Human CBL-YF005 Humanized scFv-CD28-CD3ζ Lentiviral vector T cell   Add to Cart   Datasheet
CAR-YF090 Anti-CD19 (HI19a) h(4-1BB-CD3ζ) CAR, pCDCAR1 Human HI19a Mouse scFv-4-1BB-CD3ζ Lentiviral vector T cell   Add to Cart   Datasheet
CAR-YF091 Anti-CD19 (HI19a) h(CD28-CD3ζ) CAR, pCDCAR1 Human HI19a Mouse scFv-CD28-CD3ζ Lentiviral vector T cell   Add to Cart   Datasheet
CAR-ZP021 Anti-CD19 (FMC63) h(CD28-CD3ζ) CAR, pCDCAR1 Human FMC63 Mouse scFv-CD28-CD3ζ Lentiviral vector T cell   Add to Cart   Datasheet
CAR-ZP024 Anti-CD19 (PGC3D6H10) h(CD28-CD3ζ) CAR, pCDCAR1 Human PGC3D6H10 Mouse scFv-CD28-CD3ζ Lentiviral vector T cell   Add to Cart   Datasheet
CAR-ZP047 Anti-CD19 (FMC63) h(41BB-CD3ζ) CAR, pCDCAR1 Human FMC63 Mouse scFv-4-1BB-CD3ζ Lentiviral vector T cell   Add to Cart   Datasheet
CAR-ZP050 Anti-CD19 (PGC3D6H10) h(41BB-CD3ζ) CAR, pCDCAR1 Human PGC3D6H10 Mouse scFv-4-1BB-CD3ζ Lentiviral vector T cell   Add to Cart   Datasheet
CAR-ZP3082 Anti-CD19 (FMC63) h(28-∆IL2RB-ζ(YXXQ) ) CAR, pCDCAR1 Human FMC63 Human ∆NGFR-scFv-CD28-∆IL2RB-CD3ζ-YXXQ Lentiviral vector T cell   Add to Cart   Datasheet
CAR-YF418 Anti-CD19 (SJ25C1) h(CD28-41BB-CD3ζ) CAR, pCDCAR1 Human SJ25C1 Mouse scFv-CD28-41BB-CD3ζ Lentiviral vector T Cell   Add to Cart   Datasheet
CAR-YF420 Anti-CD19 (1D3) h(-CD3ζ) CAR, pCDCAR1 Human 1D3 Mouse scFv-CD3ζ Lentiviral vector T Cell   Add to Cart   Datasheet
CAR-YF421 Anti-CD19 (1D3) h(41BB-CD3ζ) CAR, pCDCAR1 Human 1D3 Mouse scFv-41BB-CD3ζ Lentiviral vector T Cell   Add to Cart   Datasheet
CAR-YF422 Anti-CD19 (1D3) h(CD28-41BB-CD3ζ) CAR, pCDCAR1 Mouse 1D3 Mouse scFv-CD28-41BB-CD3ζ Lentiviral vector T Cell   Add to Cart   Datasheet
CAR-ZP8464 A uniCAR [Anti-GCN4 CAR], with a Fab-based CAR Adaptor [Anti-CD19 (FMC63)], a Switchable CAR System Chronic lymphocytic leukemia (CLL) Lentiviral vector   Add to Cart   Datasheet
CAR-ZP8466 A uniCAR [Anti-FITC CAR], with a Fab-based CAR Adaptor [Anti-CD19 (FMC63)], a Switchable CAR System Chronic lymphocytic leukemia (CLL) Lentiviral vector   Add to Cart   Datasheet
CAR-ZP8469 A uniCAR [Anti-GCN4 CAR (28ζ)], with a Fab-based CAR Adaptor [Anti-CD19 (1D3)], a Switchable CAR System Chronic lymphocytic leukemia (CLL) Lentiviral vector   Add to Cart   Datasheet
CAR-ZP8484 A uniCAR [Anti-biotin CAR], with a mAb-based CAR Adaptor [Anti-CD19 (Rituximab)], a Switchable CAR System Chronic lymphocytic leukemia (CLL) Lentiviral vector   Add to Cart   Datasheet
CAR-AB-ZP1 Anti-FMC63 scFv Monoclonal Antibody, FITC-Conjugated Human CAR-T Cell   Add to Cart   Datasheet
CAR-AB-ZP2 Anti-FMC63 scFv Monoclonal Antibody, Biotin-Conjugated Human CAR-T Cell   Add to Cart   Datasheet
CAR-AB-ZP3 Anti-FMC63 scFv Monoclonal Antibody, Unconjugated Human CAR-T Cell   Add to Cart   Datasheet
CAR-ZP8470 A uniCAR [Anti-GCN4 CAR (BBζ)], with a Fab-based CAR Adaptor [Anti-CD19 (1D3)], a Switchable CAR System Chronic lymphocytic leukemia (CLL) Lentiviral vector   Add to Cart   Datasheet
CAR-ZP8471 A uniCAR [Anti-GCN4 CAR(IgG4mTM/mCD28/CD3ζ)], with a Fab-based CAR Adaptor [Anti-CD19 (1D3)], a Switchable CAR System Chronic lymphocytic leukemia (CLL) Lentiviral vector   Add to Cart   Datasheet
CAR-ZP8472 A uniCAR [Anti-GCN4 CAR (IgG4mTM/mCD28/m4-1BB/ CD3ζ)], with a Fab-based CAR Adaptor [Anti-CD19 (1D3)], a Switchable CAR System Chronic lymphocytic leukemia (CLL) Lentiviral vector   Add to Cart   Datasheet
CAR-ZP8473 A uniCAR [Anti-GCN4 CAR (mCD8TM/m4-1BB/CD3ζ)], with a Fab-based CAR Adaptor [Anti-CD19 (1D3)], a Switchable CAR System Chronic lymphocytic leukemia (CLL) Lentiviral vector   Add to Cart   Datasheet
CAR-ZP8474 A uniCAR [Anti-GCN4 CAR (mCD8TM/mCD28/CD3ζ)], with a Fab-based CAR Adaptor [Anti-CD19 (1D3)], a Switchable CAR System Chronic lymphocytic leukemia (CLL) Lentiviral vector   Add to Cart   Datasheet
CAR-ZP8475 A uniCAR [Anti-GCN4 CAR (mCD28/m4-1BB/ CD3ζ)], with a Fab-based CAR Adaptor [Anti-CD19 (1D3)], a Switchable CAR System Chronic lymphocytic leukemia (CLL) Lentiviral vector   Add to Cart   Datasheet
CARP-LX-027 Anti-CD19 h(28ζ) CART, Combined with Decitabine, a CAR Plus System Human FMC63 0 CD28-CD3ζ Lentiviral vector   Add to Cart   Datasheet
CARP-LX-028 Anti-CD19 h(28ζ) CART, Combined with 1-methyl-tryptophan, a CAR Plus System Human CD28-CD3ζ Lentiviral vector   Add to Cart   Datasheet
CARP-LX-029 Anti-CD19 h(28ζ) CART, Combined with Fludarabine, a CAR Plus System Human CD28-CD3ζ Lentiviral vector   Add to Cart   Datasheet
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