CD19 Antigen in Leukemia and Lymphoma Diagnosis and Immunotherapy

Abstract

The CD19 antigen plays an important role in clinical oncology. In normal cells, it is the most ubiquitously expressed protein in the B lymphocyte lineage. CD19 expression is induced at the point of B lineage commitment during the differentiation of the hematopoietic stem cell, and its expression continues through preB and mature B cell differentiation until it is finally down-regulated during terminal differentiation into plasma cells. CD19 expression is maintained in B-lineage cells that have undergone neoplastic transformation, and therefore CD19 is useful in diagnosis of leukemias and lymphomas using monoclonal antibodies (mAbs) and flow cytometry. Interestingly, CD19 is also expressed in a subset of acute myelogenous leukemias (AMLs) indicating the close relationship between the lymphoid and myeloid lineages. Because B lineage leukemias and lymphomas rarely lose CD19 expression, and because it is not expressed in the pluripotent stem cell, it has become the target for a variety of immunotherapeutic agents, including immunotoxins. Treatment of non-Hodgkin's lymphoma (NHL) and acute lymphocytic leukemia (ALL) with anti-CD19 mAbs coupled to biological toxins has proven to be effective in vitro and in animal models, and has shown some promising results in Phase I clinical trials. Recently, the analysis of anti-CD19 effects on lymphoma cell growth has highlighted a novel mechanism of immunotherapy. Engagement of cell surface receptors like CD19 by mAbs can have anti-tumor effects by the activation of signal transduction pathways which control cell cycle progression and programmed cell death (apoptosis).

Extremely potent, rapid and costimulation‐independent cytotoxic T‐cell response against lymphoma cells catalyzed by a single‐chain bispecific antibody

“…CD19 was chosen as a target because it is an essential B-cell coreceptor expressed on a high percentage of human B-cell malignancies and on normal B cells and is established as a target for novel immunotherapeutic approaches. [25][26][27][28] In the present study, we have analyzed in detail the in vitro properties of an optimized version of bcsCD19xCD3. We conclude that bscCD19xCD3 has properties that are very distinct from those of previously developed bispecific antibodies, most notably, extreme potency, fast kinetics, independence from additional T-cell stimuli and effectiveness at low E/T ratios.…”

Immunotoxins against CD19 and CD22 are effective in killing precursor-B acute lymphoblastic leukemia cells in vitro

“…25 Most importantly, it is not present on pluripotent stem cells. 24 CD19 is also rarely lost during neoplastic transformation, 26 and it would be unusual for a patient to present with a B-lineage neoplasm that is refractory to a CD19 IT. The mean percentage expression of the CD19 antigen on our specimens was 73%, as compared to 51% for the CD22 antigen.…”

Immune Cells As Targets and Tools For Cancer Therapy

“…CD19 is the most common B cell target for engineered T cell therapies. is expressed almost exclusively on benign and most malignant B cells [14] However a common complication of CAR T cell therapy is the cytokine release syndrome (CRS), but this can be controlled with an efficient treatment e.g. anti-interleukin-6 receptor antibody [15] (Maude et al, 2014).…”