Our first candidate, CMP-001, is a combination of our Ad35K++ technology with an anti-CD-20 antibody. The 1-, 5-, and 10-year survival rates for B cell non-Hodgkins lymphoma (NHL) are 79%, 63%, and 51%, respectively. The anti-CD20 antibody rituximab has become a cornerstone of nearly all therapies for NHL. In most cases of B cell NHL recurrence, patients became resistant to rituximab therapy. Although the 5-year survival rate for B cell NHL has increased from 48% (1975-1977) to 64% (1996-2003) since the introduction of rituximab, there is still substantial room for improvement. One of the mechanisms of action of rituximab involves binding to lymphoma cells and subsequent activation of the complement system, a cascade of proteins in the blood that normally participates in the elimination of pathogens from the host. Complement activation then leads to the killing of lymphoma cells. One of the mechanisms by which lymphoma cells actively block this activity of rituximab is by up-regulating CD46 and preventing killing by the complement system. Increased levels of CD46 are found on the membranes of lymphoma cells and may contribute to the ineffectiveness of rituximab in treating NHL.
We have shown that CD46 expression on leukemia cells was more uniform and at least one order of magnitude higher than on normal PBMCs. These findings are in agreement with our previous study with samples from 38 multiple myeloma patients in which we documented that the mean CD46 receptor numbers on neoplastic plasma cells and normal hematopoietic cells were 49,130/cell and 7,340/cell, respectively. This trend is also seen in other cancers.