Comparability of Antibody-Mediated Cell Killing Activity Between a Proposed Biosimilar RTXM83 and the Originator Rituximab

HÉCTOR CUELLO; SEGATORI VALERIA INÉS; ALBERTÓ MARINA; PESCE A; ALONSO DANIEL F; GABRI MARIANO R

BIODRUGS

ADIS INT LTD

Año: 2016 vol. 30 p. 225 - 231

1173-8804

BACKGROUND: Biosimilars are described as biological products that resemble the structure of original biologic therapeutic products, with no clinically meaningful differences in terms of safety and effectiveness from the original. A wide range of biosimilars are under development or are already licensed in many countries. Biosimilars are earning acceptance and becoming a reality for immunotherapy treatments mainly based on the alternatives for the commercial anti-CD20 monoclonal antibody, rituximab. The most important mechanism of action reported for this antibody is the induction of Antibody-Dependent Cell Cytotoxicity (ADCC), which is associated with the polymorphismspresent at158positioninthe IgG receptor FcγRIIIa.OBJECTIVES: The aim of this article is to validate the functional comparability between the proposed biosimilar rituximab RTXM83 and the original product. To achieve this we will assess two of the mechanisms of action of RTXM83: Binding Capacity and ADCC induction of this biosimilar, taking into account the differentFcγRIIIa-158 polymorphisms. METHODS: Binding Capacity was evaluated by Flow Cytometry using CD20 positive cells and a wide range of antibody concentrations. The FcγRIIIa-158 polymorphisms were analyzed by PCR followed by allele-specific restriction enzyme digestion. ADCC was measured by a colorimetric LDH-release assay, using effector cells from donors with different FcγRIIIa-158 polymorphisms.RESULTS: Binding Capacity Assay showed no differences between both products. Regarding ADCC, a similar relative potency was obtained between both antibodies, showing a higher response for the valine/valine (V/V) polymorphism compared to the phenylalanine/phenylalanine (F/F), for both rituximab and RTXM83. CONCLUSION: Our data strongly suggest the biocomparability between the proposed biosimilar and the originator rituximab in antibody recognition and ADCC activity. Additionally, our results suggestthat donors with F/F polymorphism induce a lower ADCC response as it was reported.