'Modular' Leukemia Drug Shows Promise In Early Testing

A new type of engineered drug candidate has shown promise in treating chronic lymphocytic leukemia in both test tube and early animal tests, a new study shows.

The agent represents a new class of agents called small modular immunopharmaceuticals. Called CD37-SMIP, the agent targets a protein called CD37 on the surface of these leukemia cells.

The study shows that the agent can successfully attach to the protein on the leukemia cells and kill them. The agent works both by triggering the cells' self-destruction and by causing a particular class of immune cells to attack them.

In an animal model, the agent worked equally as well as the drug rituximab, now routinely used to treat chronic lymphocytic leukemia (CLL) patients. Rituximab targets a different protein on leukemia cells.

The study by researchers at the Ohio State University Comprehensive Cancer Center was published online in the journal Blood.

“Our findings have significant implications for the treatment of CLL and related malignancies,” says principal investigator John C. Byrd, director of the hematologic malignancies program at Ohio State 's James Cancer Hospital and Solove Research Institute.

Overall, Byrd says, “the findings indicate that this could be an effective agent for treating CLL and other malignancies, such as non-Hodgkin's lymphoma and acute lymphoblastic leukemia when they have expression of the CD37 protein.”

The laboratory portion of the study used CLL cells from patients, laboratory-grown non-Hodgkin's lymphoma cells and acute lymphocytic leukemia cells.

This research showed that the agent kills leukemia cells directly by triggering their self-destruction through the process of apoptosis.

The study also found that this self-destruction happens differently from how other drugs cause apoptosis. Most drugs cause cells to self-destruct by triggering a cell mechanism that requires enzymes called caspases. This new agent, however, works through a mechanism that does not require caspases.

“This is exciting because it means that this agent may benefit patients who are resistant to other CLL drugs,” says co-author Natarajan Muthusamy, a research scientist with Ohio State's Comprehensive Cancer Center. “It also suggests that it might work well in combination with other drugs, as well as alone.”

The findings also show that after the agent binds with the cancer cells, it attracts immune cells called natural killer cells, which also destroy the leukemia cells. Funding from the National Cancer Institute, the Leukemia and Lymphoma Society and the D. Warren Brown Foundation supported this research.

Trubion Pharmaceuticals, Inc., developed CD37-SMIP and provided the drug used in the study. Byrd has received no financial compensation from Trubion.

Source: Ohio State University

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.
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.
Researchers overcome chemotherapy resistance in the lab
Researchers from McGill University's Faculty of Medicine have discovered a compound that reduces resistance to chemotherapy agents used to treat cancer. Their results were published in the June issue of The Journal of Clinical Investigation (JCI).
Combination of 2 novel anti-cancer agents may help fight CML resistant to current therapy
Virginia Commonwealth University Massey Cancer Center researchers have identified that a combination of novel anti-cancer compounds is able to kill chronic myelogenous leukemia cells previously resistant to conventional forms of therapy.
In lab study, researchers find molecule that disrupts Ewing's sarcoma oncogene
Researchers at Georgetown University Medical Center have found a small molecule they say can block the action of the oncogene that causes Ewing's sarcoma, a rare cancer found in children and young adults. If further studies continue to prove beneficial, they say the novel agent could be the first targeted therapy to treat the disease, which can produce tumors anywhere in the body.
Discovery could lead to much-needed kidney failure treatment
The unwanted activation of an important cell-signaling pathway may play a role in two kidney problems that are major causes of end-stage renal disease, scientists at the Albert Einstein College of Medicine of Yeshiva University have found. Their research, which opens up a novel approach for treating kidney failure, is described in the March issue of Nature Medicine. The study was led by Dr. Katalin Susztak, an assistant professor of medicine (nephrology) at Einstein.
Daisies lead scientists down path to new leukemia drug
A new, easily ingested form of a compound that has already shown it can attack the roots of leukemia in laboratory studies is moving into human clinical trials, according to a new article by University of Rochester investigators in the journal, Blood.
Novel strategy under study for aggressive leukemia
A novel strategy to hopefully beat into oblivion one of the most aggressive forms of acute myelogenous leukemia combines the strengths of some of the newest leukemia agents, researchers say.

News discussion:

Medicine & Health news