Question

A patient has been diagnosed with lymphoma, specifically Non-Hodgkin’s Lymphoma (NHL). Lymphoma is cancer that begins in cells of the lymph system. One type of lymphoma is Non-Hodgkin’s lymphoma (NHL). There are many different types of NHL that form from different types of white blood cells (B-cells, T-cells, NK cells). Most types of NHL form from B-cells. One of the more advanced treatment for NHL in your arsenal is the use of the monoclonal antibody, Rituximab. Rituximab targets CD20 on B cells. CD20 is a signature B-cell differentiation antigen that is present through most stages of B-cell development and is ultimately lost in plasma cells.

a. Explain two way how Rituximab can kill the cells that it binds to.

b. Are there any concerns about giving this immunotherapy? Explain.

Answer 1

Rituximab mechanisms of action:-
The three major independent mechanisms are --
(1) antibody dependent cellular cytotoxicity (ADCC)
(2) complement mediated cytotoxicity (CMC)

ADCC:- Monoclonal antibodies can induce ADCC mediated by a variety of effector cells including NK cells, granulocytes and macrophages.
? These processes require that the Fc of the antibody bound to the target cell bind to Fc? receptor (Fc?Rs) on the effector cells triggering immune cell activation and death of the target cell.
?Rituximab can induce ADCC of human lymphoma cell lines by human peripheral blood mononuclear cells.

CMC:-
?CMC can clearly result in rapid cell death of rituximab-coated target cells, and is a prime mechanism of action for antibody therapy in some animal models.
??CMC occurs in patients after rituximab therapy, and that complement fixation plays a role in infusion reaction.