igm-CD20-hero-11

CD20 x CD3

CD20 is a B cell antigen that is often expressed on the surface of Non-Hodgkin’s Lymphoma (NHL) cells and Chronic Lymphocytic Leukemia (CLL) cells.

IGM’s initial therapeutic goal with our IgM CD20 x CD3 bispecific antibody is to safely and effectively treat rituximab resistant/refractory Non-Hodgkin’s Lymphoma patients. B cell mediated NHL is a group of blood cell cancers that affect the lymphatic system. The current standard of care for NHL generally includes treatment with the anti-CD20 IgG antibody rituximab (trade name Rituxan®). While this treatment is quite effective, a significant percentage of NHL patients either are initially refractory to rituximab treatment or eventually become resistant to rituximab treatment.

One of the primary factors that reduces the efficacy of rituximab treatment for certain patients is low CD20 expression on their tumor cells.1,2  Some patients enter treatment with relatively low CD20 expression on their tumors and may be initially resistant or refractory to rituximab treatment. Other patients may have early success with rituximab treatment, yet eventually develop resistance to rituximab treatment due to the loss of surface CD20 expression after rituximab therapy.

We anticipate that our anti-CD20 IgM bispecific antibody with its 10 binding units for CD20 will successfully bind to tumor cells which express relatively smaller amounts of CD20, as compared with a comparable IgG antibody which has only 2 binding units for CD20.

 

 

 

Enhanced binding of an anti-CD20 IgM as compared to a comparable anti-CD20 IgG when CD20 is displayed in vitro at relatively low density

 

IGM’s CD20 x CD3 bispecific antibody binds to both CD20 on the surface of the tumor cell and CD3 on the surface of a cytotoxic T cell. As a result of this simultaneous binding of a cytotoxic T cell and a tumor cell, the cytotoxic T cell releases cytotoxic biochemicals (perforins and granzymes) which kill the adjacent tumor cell through a very potent mechanism known as T cell directed cellular cytotoxicity (TDCC).

 

Cytotoxic T cell positioned to kill tumor cell through TDCC.

 

While CD20 x CD3 and other T cell engaging antibodies have been shown to be very potent, there have also been some safety concerns with respect to the potential for cytokine release syndrome.

In addition to better binding to low CD20 expressing tumors, IGM’s CD20 x CD3 bispecific antibody has shown to have a safer TDCC cytokine release profile, as compared to a comparable IgG CD20 x CD3 antibody.

¹Small et al. (2013) “Analysis of innate and acquired resistance to anti-CD20 antibodies in malignant B cells” Peer J, Feb 12 2013
²Taylor et al. (2010) “Antigenic Modulation and Rituxan Resistance” Seminars in Hematology, Vol 47, No 2, pp 124–132, 2010