Part:BBa_K5198000

CD19ecto

Ectodomain of human CD19 coreceptor. In its native form, CD19 is a coreceptor in the B-cell antigen receptor complex on B-lymphocytes. CD19 is used as a marker of B-cell development and is one of the most popular targets in cell therapies treating leukemia and lymphoma. This part can be used as a soluble ligand that triggers activation of receptors capable of dimerization [1]. CD19ecto has been shown to exist in monomeric and dimeric form. The dimer form is suggested to be responsible for activation of receptors.

Figure 1. Dimerization of CARs is capable of triggering receptor activation. CD19ecto is considered to trigger activation by ligand-mediated dimerization as shown [1].

The sequence was derived from human CD19 protein. The protein’s extracellular domain is responsible for binding, while the transmembrane domain anchors the protein to the cell membrane. The cytoplasmic domain plays a role in signaling pathways that influence B-cell activation and proliferation [2].

Clinical significance

CD19 is a cell surface receptor that is expressed on most B-cell malignancies. It has been shown to be expressed in normal to high levels in 80% of acute lymphoblastic leukemia (ALL), 88% of B-cell lymphomas and 100% of B-cell leukemias [3]. For this reason, CD19 has been used as a diagnostic tool to identify and track the progress of B-cell cancers [4]. More recently, CD19 has been considered a target for CAR-T cell therapies due to lack of its expression on hematopoietic stem cells and clinically manageable on-target, off-tumor toxicity resulting in B-cell aplasia [5]. CD19 targeting CAR-T products achieved exceptional response rates of up to 82% in relapsed B-cell lymphoma trials. In 2017, the FDA approved the first CAR-T product for treatment of relapsed acute lymphoblastic leukemia [6]. Sequence and Features

Assembly Compatibility:

• 10
  COMPATIBLE WITH RFC[10]
• 12
  COMPATIBLE WITH RFC[12]
• 21
  COMPATIBLE WITH RFC[21]
• 23
  COMPATIBLE WITH RFC[23]
• 25
  COMPATIBLE WITH RFC[25]
• 1000
  INCOMPATIBLE WITH RFC[1000]

  Illegal BsaI.rc site found at 225
  Illegal SapI.rc site found at 61
  

References

[1] Z. L. Chang, M. H. Lorenzini, X. Chen, U. Tran, N. J. Bangayan, and Y. Y. Chen, “Rewiring T-cell responses to soluble factors with chimeric antigen receptors,” *Nat Chem Biol*, vol. 14, no. 3, Art. no. 3, Mar. 2018, doi: [10.1038/nchembio.2565](https://doi.org/10.1038/nchembio.2565).

[2] R. H. Carter and D. T. Fearon, “CD19: Lowering the Threshold for Antigen Receptor Stimulation of B Lymphocytes,” Science, vol. 256, no. 5053. American Association for the Advancement of Science (AAAS), pp. 105–107, Apr. 03, 1992. doi: 10.1126/science.1373518.

[3] T. F. Tedder, “CD19: a promising B cell target for rheumatoid arthritis,” *Nat Rev Rheumatol*, vol. 5, no. 10, pp. 572–577, Oct. 2009, doi: [10.1038/nrrheum.2009.184](https://doi.org/10.1038/nrrheum.2009.184).

[4] K. Wang, G. Wei, and D. Liu, “CD19: a biomarker for B cell development, lymphoma diagnosis and therapy,” *Exp Hematol Oncol*, vol. 1, p. 36, Nov. 2012, doi: [10.1186/2162-3619-1-36](https://doi.org/10.1186/2162-3619-1-36).

[5] B. C. Miller and M. V. Maus, “CD19-Targeted CAR T Cells: A New Tool in the Fight against B Cell Malignancies,” *Oncology Research and Treatment*, vol. 38, no. 12, pp. 683–690, Nov. 2015, doi: [10.1159/000442170](https://doi.org/10.1159/000442170).

[6] R. Awasthi, H. J. Maier, J. Zhang, and S. Lim, “Kymriah® (tisagenlecleucel) – An overview of the clinical development journey of the first approved CAR-T therapy,” *Hum Vaccin Immunother*, vol. 19, no. 1, p. 2210046, doi: [10.1080/21645515.2023.2210046](https://doi.org/10.1080/21645515.2023.2210046).