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Assessment of physicochemical properties of rituximab related to its immunomodulatory activity.

Miranda-Hernández MP, López-Morales CA, Ramírez-Ibáñez ND, Piña-Lara N, Pérez NO, Molina-Pérez A, Revilla-Beltri J, Flores-Ortiz LF, Medina-Rivero E - J Immunol Res (2015)

Bottom Line: The immunomodulatory activity of rituximab is closely related to critical quality attributes that characterize its chemical composition and spatial configuration, which determine the recognition of CD20 and the binding to receptors or factors involved in its effector functions, while regulating the potential immunogenic response.The evaluation of anti-chimeric antibodies did not show differential immunogenicity among products.Overall, these data confirm that similarity of critical quality attributes results in a comparable immunomodulatory activity.

View Article: PubMed Central - PubMed

Affiliation: Unidad de Investigación y Desarrollo, Probiomed S.A. de C.V., Cruce de carreteras Acatzingo-Zumpahuacán, 52400 Tenancingo de Degollado, MEX, Mexico.

ABSTRACT
Rituximab is a chimeric monoclonal antibody employed for the treatment of CD20-positive B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis and microscopic polyangiitis. It binds specifically to the CD20 antigen expressed on pre-B and consequently on mature B-lymphocytes of both normal and malignant cells, inhibiting their proliferation through apoptosis, CDC, and ADCC mechanisms. The immunomodulatory activity of rituximab is closely related to critical quality attributes that characterize its chemical composition and spatial configuration, which determine the recognition of CD20 and the binding to receptors or factors involved in its effector functions, while regulating the potential immunogenic response. Herein, we present a physicochemical and biological characterization followed by a pharmacodynamics and immunogenicity study to demonstrate comparability between two products containing rituximab. The physicochemical and biological characterization revealed that both products fit within the same response intervals exhibiting the same degree of variability. With regard to clinical response, both products depleted CD20+ B-cells until posttreatment recovery and no meaningful differences were found in their pharmacodynamic profiles. The evaluation of anti-chimeric antibodies did not show differential immunogenicity among products. Overall, these data confirm that similarity of critical quality attributes results in a comparable immunomodulatory activity.

No MeSH data available.


Related in: MedlinePlus

Sequence coverage of the heavy and light chain of the reference product.
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Related In: Results  -  Collection


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fig3: Sequence coverage of the heavy and light chain of the reference product.

Mentions: For both products sequence verification, expressed as MS/MS sequence coverage, exceeded the accepted consensus value of 90%, being 98.7% and 98.6% for Kikuzubam and 98.7% and 97.2% for the reference product of their heavy and light chains, respectively (Figures 2 and 3).


Assessment of physicochemical properties of rituximab related to its immunomodulatory activity.

Miranda-Hernández MP, López-Morales CA, Ramírez-Ibáñez ND, Piña-Lara N, Pérez NO, Molina-Pérez A, Revilla-Beltri J, Flores-Ortiz LF, Medina-Rivero E - J Immunol Res (2015)

Sequence coverage of the heavy and light chain of the reference product.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4418000&req=5

fig3: Sequence coverage of the heavy and light chain of the reference product.
Mentions: For both products sequence verification, expressed as MS/MS sequence coverage, exceeded the accepted consensus value of 90%, being 98.7% and 98.6% for Kikuzubam and 98.7% and 97.2% for the reference product of their heavy and light chains, respectively (Figures 2 and 3).

Bottom Line: The immunomodulatory activity of rituximab is closely related to critical quality attributes that characterize its chemical composition and spatial configuration, which determine the recognition of CD20 and the binding to receptors or factors involved in its effector functions, while regulating the potential immunogenic response.The evaluation of anti-chimeric antibodies did not show differential immunogenicity among products.Overall, these data confirm that similarity of critical quality attributes results in a comparable immunomodulatory activity.

View Article: PubMed Central - PubMed

Affiliation: Unidad de Investigación y Desarrollo, Probiomed S.A. de C.V., Cruce de carreteras Acatzingo-Zumpahuacán, 52400 Tenancingo de Degollado, MEX, Mexico.

ABSTRACT
Rituximab is a chimeric monoclonal antibody employed for the treatment of CD20-positive B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis and microscopic polyangiitis. It binds specifically to the CD20 antigen expressed on pre-B and consequently on mature B-lymphocytes of both normal and malignant cells, inhibiting their proliferation through apoptosis, CDC, and ADCC mechanisms. The immunomodulatory activity of rituximab is closely related to critical quality attributes that characterize its chemical composition and spatial configuration, which determine the recognition of CD20 and the binding to receptors or factors involved in its effector functions, while regulating the potential immunogenic response. Herein, we present a physicochemical and biological characterization followed by a pharmacodynamics and immunogenicity study to demonstrate comparability between two products containing rituximab. The physicochemical and biological characterization revealed that both products fit within the same response intervals exhibiting the same degree of variability. With regard to clinical response, both products depleted CD20+ B-cells until posttreatment recovery and no meaningful differences were found in their pharmacodynamic profiles. The evaluation of anti-chimeric antibodies did not show differential immunogenicity among products. Overall, these data confirm that similarity of critical quality attributes results in a comparable immunomodulatory activity.

No MeSH data available.


Related in: MedlinePlus