Human CD19 x Human CD3 Bispecific Antibody

CD19

The cluster of differentiation 19 (CD19) is a transmembrane protein acting as a co-receptor for the B cell receptor (BCR) modulating B lymphocyte differentiation and activation [1]. CD19 is expressed throughout the entire B cell maturation process and can be found in most lymphoid malignancies including acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL) and Non-Hodgkin lymphoma (NHL). Therefore, CD19 is an interesting target for the development of experimental therapeutic agents in immunotherapy research [2].

In 2014, the first bispecific T-cell engager (BiTE^®) blinatumomab was approved by the FDA as the second line treatment of refractory ALL. By simultaneously binding to hCD3 and hCD19, blinatumomab (AMG103) engages unstimulated T cells to proliferate and exert cytotoxic activity on CD19-positive lymphoma cells [3].
 

CD3

The cluster of differentiation 3 (CD3, formerly named T3) is a multimeric protein complex consisting of four polypeptides (CD3ε, CD3γ, CD3δ, and CD3ζ) that assemble as three dimers (εγ, εδ, and ζζ) [4]. It is a marker of T cells, which recognizes and participates in the elimination of infected cells and tumor cells through the interaction between the TCR (T cell receptor) on T cells and the MHC-peptide complex on antigen-presenting cells [4-5]. Because of its short cytoplasmic tail, the TCR lacks the ability to signal and requires non-covalent association with the CD3. Upon antigen recognition, the TCR/CD3 complex on T cells triggers downstream intracellular signaling and participates in T cell activation [4].

1. Del Nagro et al., 2005. CD 19 function in central and peripheral B-cell development. Immunol Res 31, 119–131 (2005).
2. Katz, Ben-Zion; Herishanu, Yair, 2014. Therapeutic targeting of CD19 in hematological malignancies: past, present, future and beyond. Leukemia & Lymphoma, 55(5), 999–1006.
3. Zinzani, P.L., Minotti, G., 2022.  Anti-CD19 monoclonal antibodies for the treatment of relapsed or refractory B-cell malignancies: a narrative review with focus on diffuse large B-cell lymphoma. J Cancer Res Clin Oncol 148, 177–190.
4. Chetty R. & Gatter K., 1994. CD3: structure, function, and role of immunostaining in clinical practice. J. Pathol. 173(4):303-307.
5. Smith-Garvin J.E. et al., 2009. T Cell Activation. Ann. Rev. Immunol. 27:591-619.3.