Gene therapy protocol activates immune system in patients with leukemia

A research team at the Moores Cancer Center at University of California, San Diego (UCSD) reports that patients with chronic lymphocytic leukemia (CLL) who were treated with a gene therapy protocol began making antibodies that reacted against their own leukemia cells. The study will be published on line the week of February 11-15 in the online edition of the Proceedings of the National Academy of Science.

Researchers led by Thomas J. Kipps, M.D., Ph.D., inserted a gene with the potential to activate an immune response – a gene therapy protocol developed at UCSD – into six patients with CLL, the most common form of adult leukemia. Several of the patients started making antibodies that reacted against their own leukemia cells. When tested in the lab, the antibodies also reacted with the leukemia cells of other patients with the disease.

“The patient’s own leukemia cells were modified outside of their body and given back as a vaccine,” said Kipps. “The result raises hope that it may be possible to activate a patient’s immune system against their own cancer.”

The patients were shown to make antibodies reactive with a leukemia-associated antigen – a protein made by leukemia cells that can stimulate the body's immune system to produce antibodies – called ROR1. This antigen appears to be found only on the cell surface of the leukemia cells, but not on normal cells, and serves as a receptor that binds to a ligand called Wnt5a, which activates a pathway important for the survival of the leukemia cells.

“The Wnt5a ligand interacts with ROR1 to enhance leukemia-cell survival. Antibodies that react with ROR1 can interfere with this survival signal and might also specifically target the leukemia cells for destruction,” Kipps said.

He also noted that because the ROR1 antigen is found only on leukemia cells, it could be developed as a very specific marker to monitor for the continued presence of leukemia cells after treatment or for identifying leukemia cells in patients with early disease, when the cancer otherwise might not be detected. It also provides a much more specific target for antibody therapy. Antibodies that target ROR1 would be unlike currently used antibodies, which bind antigens found not only on leukemia cells, but also on normal cells. Because they can destroy normal cells, the antibodies currently used to treat patients with this leukemia can cause side-effects and weaken the immune system.

The ROR1 antigen is ordinarily found on a few cells in early embryonic development and is not detected on adult human cells or tissues. However, high amounts of this antigen are found on all the leukemia cells of patients with CLL. In the PNAS paper, the UCSD researchers present data on the leukemia cells of approximately 70 patients, all of which expressed the ROR1 antigen.

Source: University of California - San Diego

Related stories:

Researchers devise means to create blood by identifying earliest stem cells
Johns Hopkins researchers have discovered the earliest form of human blood stem cells and deciphered the mechanism by which these embryonic stem cells replicate and grow. They also found a surprising biological marker that pinpoints these stem cells, which serve as the progenitors for red blood cells and lymphocytes.
Scientists replicate diseases in the lab with new stem cell lines
A set of new stem cell lines will make it possible for researchers to explore ten different genetic disorders—including muscular dystrophy, juvenile diabetes, and Parkinson's disease—in a variety of cell and tissue types as they develop in laboratory cultures.
Cancer drug shows promise against graft vs. host disease
A new University of Michigan study in mice suggests that a drug recently approved to fight cancer tumors is also able to reduce the effects of graft-versus-host disease, a common and sometimes fatal complication for people who have had bone marrow transplants.
Not the protein, but its location in the cell, determines the onset of leukemia
Scientists are still searching for the cause of many forms of Leukemia, including T-cell acute lymphoblastic leukemia. VIB researchers connected to the Katholieke Universiteit Leuven have discovered that the carcinogenic property of the fusion protein NUP214-ABL1 largely depends on its location in the cell. Casting new light on the biological processes behind T-ALL, this finding is important in the search for new targeted therapies that are less toxic than chemotherapy.
Activation of LYN kinase is associated with imatinib-resistance in CML patients
Activation of LYN kinase is associated with resistance to imatinib (Gleevec) in patients with chronic myelogenous leukemia (CML), researchers report in the June 24 online issue of the Journal of the National Cancer Institute.
Math could help cure leukemia
When kids complain that math homework won't help them in real life, a new answer might be that math could help cure cancer.


Gene mutation improves leukemia drug's effect
Gene mutations that make cells cancerous can sometimes also make them more sensitive to chemotherapy. A new study led by cancer researchers at Ohio State University shows that a mutation present in some cases of acute leukemia makes the disease more susceptible to high doses of a particular anticancer drug.
Immune molecule that plays a powerful role in avoiding organ rejection identified
When a mouse's immune system is deciding whether to reject a skin graft, one powerful member of a molecular family designed to provoke such a response can effectively reduce the visibility of the mouse's own cells and help the graft survive, researchers say.

News discussion:

Medicine & Health news