With assistance from donations to the BCRF, we are developing novel treatments for patients with chronic lymphocytic leukemia (CLL) that target ROR1, a protein that we recently found is an “oncofetal antigen” in CLL.
We investigated the blood samples of CLL patients who received cell vaccines composed of their own leukemia cells that had been modified to improve their capacity to stimulate anti-leukemia immune responses. We found that some of the patients treated with these vaccines made antibodies that specifically bound to their own leukemia cells and the leukemia cells of other patients. They did not however, react with other cells. The antibodies appeared specific for leukemia cells! Because of this finding, these antibodies appear to be highly specific anti-leukemia antibodies.
Our lab has also learned that these anti-leukemia antibodies bind to a protein called ROR1. ROR1 had previously been found on the surface of some cells in the fetus, suggesting that it might play a role in early development. After birth, the expression of ROR1 drops to negligible levels. We made monoclonal antibodies that could also bind to ROR1. Using these antibodies, we found that ROR1 was on the surface of leukemia cells from nearly all patients examined, but not on other cells or the cells of healthy adults. In contrast to rituximab or Campath, which bind leukemia cells and normal lymphocytes, the anti-ROR1 antibodies bound only to leukemia cells. Because ROR1 is only found on fetal cells and on cancer cells, it can be considered an “onco-fetal antigen”.
In the lab we currently are investigating whether the antibodies that bind to ROR1 can be used in the treatment of CLL. If found effective, then anti-ROR1 antibodies potentially could be used to treat patients with CLL, providing a more specific and effective treatment than other antibodies in use for leukemia treatment. Such treatment might not affect normal B cells or T cells, which are important for our immune function.
Our lab is actively pursuing the most effective method for creating a ROR1 vaccine that can induce immune responses against ROR1. This method of could be quite effective in clearing leukemia cells from the body and/or in preventing recurrent disease after therapy. If found safe and effective, we might be able to give ROR1 vaccines to patients before they ordinarily would require chemotherapy. This exciting advance could potentially eliminate the need for treatment with currently used anti-leukemia drugs or monoclonal antibodies that can damage the marrow or adversely effect our ability to mount our immune response to infection.