Human CD20 Antibody - Rituximab IgG4 (S228P) Isotype

Human IgG4 (S228P) engineered monoclonal antibody (mAb) against human CD20

Anti-hCD20-hIgG4 (S228P) features the variable region of rituximab and a mutated constant region of the human IgG4 isotype reported to reduce Fab-arm exchange [1].

Rituximab is a mouse/human chimeric monoclonal antibody that targets the CD20 antigen found on the surface of malignant and normal B lymphocytes.

The binding of rituximab to CD20 results in cell destruction through different mechanisms including direct signaling of apoptosis, complement activation, and cell-mediated cytotoxicity.

Rituximab has been approved by the FDA to treat various lymphoid malignancies, including B-cell non-Hodgkin's lymphoma and B-cell chronic lymphocytic leukemia.

Anti-hCD20-hIgG4 (S228P) is an engineered human IgG4 isotype. IgG4 antibodies display low antibody-dependent cell-mediated cytotoxicity (ADCC) and no complement-dependent cytotoxicity (CDC).

IgG4s are dynamic molecules that exchange Fab arms by swapping a heavy chain and attached light chain (half molecule) with a heavy-light chain pair from another molecule, resulting in bispecific antibodies [1-2].

IgG4 molecules thereby lose their ability to cross-link antigens and to form immune complexes under most conditions [2]. Thus, mutations that prevent Fab-arm exchange in vivo should be considered when designing therapeutic IgG4. The constant region of Anti-hCD20-hIgG4 (S228P) contains the S228P mutation which reduces Fab-arm exchange by stabilizing the disulfides in the core-hinge of the IgG4 molecules [1].

Anti-hCD20-hIgG4 (S228P) was generated by recombinant DNA technology. It has been produced in Chinese hamster ovary (CHO) cells and purified by affinity chromatography with protein G.

More isotypes of this antibody are available and can be used for comparison of biological activities such as ADCC (see below or in the 'upon request' section). InvivoGen also provides type I and type II anti-hCD20 mAbs featuring the variable regions of Ofatumumab or Obinutuzumab, with either native or engineered Fc regions.

References:

1. Labrijn AF. et al., 2009. Therapeutic IgG4 antibodies engage in Fab-arm exchange with endogenous human IgG4 in vivo. Nat Biotechnol. 27(8):767-71.
2. van der Neut Kolfschoten M. et al., 2007. Anti-inflammatory activity of human IgG4 antibodies by dynamic Fab arm exchange. Science. 317(5844):1554-7.