BACKGROUND AND CHALLENGES

Non-Hodgkin lymphoma and Hodgkin lymphoma are a group of cancers originating from the lymphatic system (a part of the immune system). In 2009, more than 70,000 new cases of lymphoma were diagnosed in the United States, and non Hodgkin lymphoma alone is the fifth most common cancer in women. Lymphoma is mainly a cancer of adults, but children are not spared. In fact, lymphoma is the third most common cancer in children under 15, accounting for about 8% of all new childhood cancer cases every year. The available treatment options are not effective enough, and more than 20,000 children and adults lost their battle against this lethal disease in 2009 alone.

SEARCHING FOR LIFE-SAVING TREATMENTS

The National Foundation for Cancer Research supports leading cancer researchers who are dedicated to bringing more effective, life-saving treatments to patients with lymphoma. With long term support from NFCR, three outstanding scientists are developing novel immunotherapy, seeking innovative strategies to improve existing therapy, and developing a more personalized approach to treating lymphoma.

Developing novel immunotherapy to treat lymphoma is the goal of NFCR Project Director Laurence J.N. Cooper, M.D., Ph.D., at M.D. Anderson Cancer Center. The human immune system is powerful when it comes to in battling against invaders like bacteria, but it is very often no match for cancer cells. Cancer cells are able to trick the immune system, escape immune surveillance and grow and spread under the radar, so to speak. But the game may end soon for certain types of lymphoma and leukemia. Dr. Cooper and his team have developed a cutting-edge technique which can genetically re-program a patient's T cells-the leading cells among all immune cells when it comes to combating cancer. These re-engineered T cells, installed with a molecular sensor, can detect a specific target molecule called CD19 that sits on the cells of non-Hodgkin lymphoma and certain types of leukemia. Once locked onto their targets, the re-engineered T cells will mount a full-blown attack to eliminate those cancer cells. This novel immunotherapy was so effective in laboratory testing that it is currently being evaluated in a Phase I clinical trial in patients with CD19+ lymphoma.

To make this new immunotherapy more useful in the clinic, Dr. Cooper is now developing technology that allows for quick and cost-effective manufacturing of these therapeutic T cells. This is a crucial step for moving this novel therapy into clinical applications. Dr. Cooper's innovative treatment approach may soon enter the next level of clinical development and provide doctors and patients a new weapon to use in their fight against lymphoma and leukemia.

Conquering the lethal complications of bone marrow transplantation. Bone marrow transplantation is a life-saving procedure used in patients with lymphoma to replenish their vital blood-forming system which is often destroyed by high dose chemotherapy or radiation. One way to obtain healthy bone marrow cells is from a matched donor (allogeneic transplant). Research has shown that a donor's transplant not only helps to replenish the patient's (recipient's) blood-forming system, but also helps fight any remaining lymphoma cells in that patient through an immune reaction. But this can be a double-edged sword because the transplant may also cause a severe complication known as the graft-versus-host disease (GVHD). In GVHD, a subset of the immune cells from a donor's transplant is activated and mounts vigorous immunologic attacks on the patient's tissues. This side effect could be lethal, and that greatly limits the clinical application of allogeneic bone marrow transplantation. NFCR Fellow Curt Civin, M.D., at the University of Maryland School of Medicine (formerly at Johns Hopkins University), is seeking ways to reduce the lethal side effects of this treatment, making it safer and more beneficial for patients.

Researchers have found that when the "anti-recipient" immune cells from a donor's transplant are activated and ready to attack their new host (the patient), there are molecular changes in the cell signaling pathways that also render these cells susceptible to death. Dr. Civin and his team developed a unique strategy which takes advantage of this vulnerability and sends the anti-recipient immune cells onto their own suicidal path. This innovative strategy also keeps intact the "recipient-friendly" cells from the transplant, which is essential for successful blood replenishment in the patient. With continued support, Dr. Civin will further evaluate this exciting new approach in his research laboratory. He hopes to bring this promising treatment strategy to patients in the near future, saving more lives of those with lymphoma and other
diseases.

Tailoring a new anti-cancer drug to the right patients. CloretazineTM is a promising new anti-cancer drug currently being tested clinically in patients with lymphoma (non-Hodgkin and Hodgkin), leukemia, brain tumors, and other types of cancer. Results from an earlier clinical trial for treatment of leukemia showed that Cloretazine works very well in 30% of patients. To make the wisest and best use of this new drug, doctors need to be able to predict drug response in individual patients, and only prescribe the drug to those who are most likely to benefit from it. If physicians could be empowered with such a reliable diagnostic tool, this would also signifi cantly benefit the rest of the patients by saving them precious time to pursue other treatment options that might be more effective for them than Chloretazine.

Developing a reliable assay for predicting drug response requires a clear understanding of how that drug works. No one knows Chloretazine better than its designer, NFCR Project Director Alan Sartorelli, Ph.D., from the Yale University School of Medicine. By taking advantage of the unique molecular mechanism of this drug, Dr. Sartorelli was able to develop a method for quantitatively measuring the level of a protein called AGT in tumor cells (the AGT assays). Only patients whose tumor cells contain low levels of AGT are likely to respond to Cloretazine. Laboratory tests using cultured cancer cells prove that this new method is simple and accurate, making it very suitable for clinical application. Next, Dr. Sartorelli will evaluate the AGT assays in human tumor samples, moving personalized Cloretazine treatment one step closer for patients with lymphoma and other types of cancer.

NEXT STEPS: HOW YOU CAN HELP

These NFCR-supported research projects hold great promise for developing new and better treatments to save
more patients' lives from lymphoma. With more money, however, they could ramp up their
efforts and accelerate progress.  Please click here if you would like to make a donation.