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Anti-CD19 Monoclonal Antibodies: a New Approach to Lymphoma Therapy.

Naddafi F, Davami F - Int J Mol Cell Med (2015)

Bottom Line: CD19 is expressed on B- lineage cells and follicular dendritic cells and plays a key role in B cell malignancies and autoimmune diseases.Thus, it has been considered as potential target for several monoclonal antibodies (mAbs).For decades, chemotherapy has been known as one of the major antitumor therapies eradicating high proliferative tumor cells.

View Article: PubMed Central - PubMed

Affiliation: Pharmaceutical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

ABSTRACT
CD19 is expressed on B- lineage cells and follicular dendritic cells and plays a key role in B cell malignancies and autoimmune diseases. Thus, it has been considered as potential target for several monoclonal antibodies (mAbs). For decades, chemotherapy has been known as one of the major antitumor therapies eradicating high proliferative tumor cells. But, anti- CD19 mAbs developed for treating CD19- positive lymphomas and autoimmune diseases would rank among the most novel area of research and development in the pharmaceutical industry. Moreover, several anti- CD19 mAbs are currently being tested in various clinical trials and this review provides an overview of the research accomplished so far.

No MeSH data available.


Related in: MedlinePlus

Anti CD19 mAbs types
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Figure 1: Anti CD19 mAbs types

Mentions: Acute leukemia is considered as the most common form of childhood malignancies (1), accounting for 20–30% of all pediatric malignan-cies depending on age (2). In the United States, about 2500 new patients are diagnosed annually; and 80% of these patients are B-lineage acute lymphoblastic leukemia (B-ALL) (1). In western countries, high incidence rates of non–Hodgkin's lymphoma (NHL) have been reported, and most of NHL subtypes are more prevalent among men than women (3). The fifth most common cancer in the United States is NHL and >66,000 patients have been diagnosed with NHL in 2008 (4). NHL is accounting for about 4% of all cancer diagnoses in incidence and deaths annually (5). CD19 is a 95- kDa transmembrane glycoprotein which belongs to the immunoglobulin (Ig) superfamily and can act as a central positive response regulator in B cells (6, 7). The CD19 has been expressed on the surface of leukemia cells in > 90% of cases with acute lymphoblastic leukemia (ALL). Moreover, it can be expressed on tumor cells of cases with both B-cell NHL and chronic lymphocytic leukemia (CLL). Thus, CD19 antigen is an ideal target for immunotherapy of B-cell malignancies (8, 9). CD19 can act as a B cell co-receptor in conjunction with both CD21 and CD81 (10). Genetic studies show that CD19 has a role in keeping a balance between immunity and autoimmunity (10). Although both CD19 and CD22 have their own regulatory network, they do not modulate B cell receptor (BCR) signals independently. CD19 modulates CD22 phoshoryla-tion by increasing Lyn kinase activity, while CD22 suppresses CD19 phosphorylation through SH-protein tyrosine phosphatase-1 (SHP-1). This ‘‘CD19/CD22 loop’’ could be directly related to an autoimmune phenotype in mice, so that it could be an attractive therapeutic target for regulating B cell signaling in autoimmune diseases (7). Although various antibody-based therapies targeting CD20 including rituxan® (rituximab) are on the market (11), anti CD19 monoclonal antibodies (mAbs) have lately been advanced into clinical trials. Many anti-CD19 IgG1 antibodies with cytotoxicity-improved Fcγ part and three drug conjugated antibodies including coltuximabravta-nsine (SAR3419), denintuzumab-mafodotin and taplitu-momabpaptox are now in phase 1/2 trials (5, 12) and the most advanced is the anti-CD19/CD3 BiTE antibody blinatumumab, which is in phase 1 trial in patients with NHL (13, 14) and was approved for Precursor B-cell acute lymphoblastic leukemia (B-cell ALL) on December 3, 2014 (12). Antibody drug conjugates (ADCs) comprise an antibody which is joined to a cytotoxic drug by a linker. ADCs could join the specificity of a monoclonal antibody (mAb) to the cytotoxicity of a small molecule drug .Thus, they are promising new therapeutic anticancer drugs. Currently, there are over 30 ADCs that are being investigated in early or late stage of clinical trials (15) (Table 1) (Fig. 1, 2).


Anti-CD19 Monoclonal Antibodies: a New Approach to Lymphoma Therapy.

Naddafi F, Davami F - Int J Mol Cell Med (2015)

Anti CD19 mAbs types
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4644525&req=5

Figure 1: Anti CD19 mAbs types
Mentions: Acute leukemia is considered as the most common form of childhood malignancies (1), accounting for 20–30% of all pediatric malignan-cies depending on age (2). In the United States, about 2500 new patients are diagnosed annually; and 80% of these patients are B-lineage acute lymphoblastic leukemia (B-ALL) (1). In western countries, high incidence rates of non–Hodgkin's lymphoma (NHL) have been reported, and most of NHL subtypes are more prevalent among men than women (3). The fifth most common cancer in the United States is NHL and >66,000 patients have been diagnosed with NHL in 2008 (4). NHL is accounting for about 4% of all cancer diagnoses in incidence and deaths annually (5). CD19 is a 95- kDa transmembrane glycoprotein which belongs to the immunoglobulin (Ig) superfamily and can act as a central positive response regulator in B cells (6, 7). The CD19 has been expressed on the surface of leukemia cells in > 90% of cases with acute lymphoblastic leukemia (ALL). Moreover, it can be expressed on tumor cells of cases with both B-cell NHL and chronic lymphocytic leukemia (CLL). Thus, CD19 antigen is an ideal target for immunotherapy of B-cell malignancies (8, 9). CD19 can act as a B cell co-receptor in conjunction with both CD21 and CD81 (10). Genetic studies show that CD19 has a role in keeping a balance between immunity and autoimmunity (10). Although both CD19 and CD22 have their own regulatory network, they do not modulate B cell receptor (BCR) signals independently. CD19 modulates CD22 phoshoryla-tion by increasing Lyn kinase activity, while CD22 suppresses CD19 phosphorylation through SH-protein tyrosine phosphatase-1 (SHP-1). This ‘‘CD19/CD22 loop’’ could be directly related to an autoimmune phenotype in mice, so that it could be an attractive therapeutic target for regulating B cell signaling in autoimmune diseases (7). Although various antibody-based therapies targeting CD20 including rituxan® (rituximab) are on the market (11), anti CD19 monoclonal antibodies (mAbs) have lately been advanced into clinical trials. Many anti-CD19 IgG1 antibodies with cytotoxicity-improved Fcγ part and three drug conjugated antibodies including coltuximabravta-nsine (SAR3419), denintuzumab-mafodotin and taplitu-momabpaptox are now in phase 1/2 trials (5, 12) and the most advanced is the anti-CD19/CD3 BiTE antibody blinatumumab, which is in phase 1 trial in patients with NHL (13, 14) and was approved for Precursor B-cell acute lymphoblastic leukemia (B-cell ALL) on December 3, 2014 (12). Antibody drug conjugates (ADCs) comprise an antibody which is joined to a cytotoxic drug by a linker. ADCs could join the specificity of a monoclonal antibody (mAb) to the cytotoxicity of a small molecule drug .Thus, they are promising new therapeutic anticancer drugs. Currently, there are over 30 ADCs that are being investigated in early or late stage of clinical trials (15) (Table 1) (Fig. 1, 2).

Bottom Line: CD19 is expressed on B- lineage cells and follicular dendritic cells and plays a key role in B cell malignancies and autoimmune diseases.Thus, it has been considered as potential target for several monoclonal antibodies (mAbs).For decades, chemotherapy has been known as one of the major antitumor therapies eradicating high proliferative tumor cells.

View Article: PubMed Central - PubMed

Affiliation: Pharmaceutical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

ABSTRACT
CD19 is expressed on B- lineage cells and follicular dendritic cells and plays a key role in B cell malignancies and autoimmune diseases. Thus, it has been considered as potential target for several monoclonal antibodies (mAbs). For decades, chemotherapy has been known as one of the major antitumor therapies eradicating high proliferative tumor cells. But, anti- CD19 mAbs developed for treating CD19- positive lymphomas and autoimmune diseases would rank among the most novel area of research and development in the pharmaceutical industry. Moreover, several anti- CD19 mAbs are currently being tested in various clinical trials and this review provides an overview of the research accomplished so far.

No MeSH data available.


Related in: MedlinePlus