Novel Antibody May Restore Immune Response to Rituximab for CLL

Among a group of patients with chronic lymphocytic leukemia who were previously unresponsive to rituximab, a new antibody could help enable the immune system to attack the cancer cells.

Rituximab, a monoclonal antibody, is a common treatment for chronic B cell lymphocytic leukemia (B-CLL), and can be used either on its own or in conjunction with chemotherapy. Although a successful therapy in some patients, rituximab appears to be ineffectual in others, which prior research has indicated may be due to their having certain complement regulatory proteins like the soluble protective protein complement factor H (CFH), which can insulate cancer cells from the cytotoxic effects of rituximab.

Researchers identified a small group of 11 patients with B-CLL who had not yet received therapy and tested their B cells to determine whether they showed a response to rituximab. They then administered a novel antibody for CFH to observe if it resulted in cytotoxic response. Their findings were published in PLOS One.

Of the 11 participants, 10 did not show a tumor cell response when rituximab was administered to the cells. After adding the CFH antibody to rituximab, however, 5 of 11 (45%) showed significant increases in cytotoxic response. In these 5 “augmentable responders,” adding the CFH antibody to rituximab enhanced cytotoxic response within the cancer cells by 1.5- to 2.5-fold.

Senior author Edward F. Patz, Jr, MD, summed up these findings in a press release from Duke Cancer Institute, where he is the James and Alice Chen Professor of Radiology.

Rituximab “works in part through an immune mechanism that triggers cancer cells to die. In some people, this immune mechanism is de-activated. Our antibody basically re-activates it,” Patz explained. “This is a combination approach, and it appears to strip away immune protection of cancer cells. Patients who had been rituximab resistant became rituximab sensitive.”

In the study, the researchers acknowledged that over half of the sample did not show a response to the CFH antibody, which indicates that there are many routes by which cancer cells can evade being killed by therapy, so “understanding each of these potential inhibitory mechanisms will be required to achieve a relevant therapeutic response.”

The study authors called for further research on the efficacy and safety of the CFH antibody in combination with rituximab for patients with B-CLL and similar cancers. Such trials would also provide more data on tumor cells’ complex immune defenses against therapy, which is essential as “a better understanding of resistance mechanisms will help optimize cancer therapy,” they write.