New Treatment for Drug-Resistant Acute Lymphoblastic Leukemia Tested Successfully
Overview of Acute Lymphoblastic Leukemia
Acute lymphoblastic leukemia (ALL) is the most prevalent cancer among children, contributing to approximately 20% of adult leukemia cases. Despite the availability of several therapies that enhance survival rates, some patients still face disease recurrence, while others find these treatments ineffective.
Development of a New Mouse Model
Researchers from Case Western Reserve University School of Medicine have developed a novel mouse model specifically to study drug-resistant acute lymphoblastic leukemia. They extracted cancer cells from individuals diagnosed with drug-resistant ALL and transplanted these cells into mice to create a representative model of the disease.
Pre-Treatment Observations
During their observations, the researchers noted that as the cancer progressed, both tumor cells and surrounding cells in the tumor microenvironment produced molecules that inhibited the activity of natural immune cells. A significant presence of TGF-beta, an inhibitory molecule, was detected in the bloodstream of the new mouse model. Further analysis revealed that the cancer cells were the source of TGF-beta, which accumulated in the microenvironment, shielding the tumor from natural immune killer cells. Consequently, the cancer cells exhibited nearly double the survival rate.
Innovative Treatment Development
In response to these findings, the researchers devised a new treatment targeting drug-resistant acute lymphoblastic leukemia that enhanced the capacity of natural immune killer cells to eliminate cancer cells. The results of their study were published in the journal *Cancer Immunology Research*.
Mechanism of Action of the New Treatment
The treatment involved a specially designed antibody that marked acute lymphoblastic leukemia cells, attracting natural immune killer cells (B-cell Activating Factor, or BAFF-R). BAFF-R served as a connector between cancer cells and immune cells, allowing the natural killer cells to attach to the antibody and subsequently destroy the cancer cells. The antibody was administered 30 minutes after treatment and remained effective for two days. To improve the antibody’s efficacy, the researchers incorporated a second anti-tumor molecule (CD16) to assist natural immune killer cells in accurately locating BAFF-R.
Effectiveness of the New Treatment
Initial tests on the new mouse model focused on the treatment’s efficacy using a single antibody. The findings indicated that administering antibodies to mice in the early stages of the disease nearly eradicated leukemia cells. However, in more advanced stages, when the tumor had established its microenvironment, the antibody alone proved insufficient.
“The tumor microenvironment had a clear negative impact on the natural killer cell’s ability to kill, which led us to incorporate a TGF-beta receptor inhibitor into our antibody treatment,” stated the main investigator.
The combination of the antibody and TGF-beta receptor inhibitor demonstrated improved treatment effectiveness, even in later stages. This approach enhanced the capacity of natural immune killer cells to eliminate leukemia by up to 35%. The testing involved mice injected with acute lymphoblastic leukemia cells from four distinct patients.
Future Implications
The researchers are optimistic that their innovative treatment for drug-resistant acute lymphoblastic leukemia will provide significant benefits to patients whose leukemia does not respond to existing treatment options.
References
Vicioso, Y., Gram, H., Beck, R., Asthana, A., Zhang, K., Wong, D., Letterio, J., and Parameswaran, R. (2019). Combination Therapy for Treating Advanced Drug-Resistant Acute Lymphoblastic Leukemia. *Cancer Immunology Research*, 7(7), pp.1106-1119.
EurekAlert!. (2019). Researchers discover therapy to treat drug-resistant acute lymphoblastic leukemia. [online] Available at: https://www.eurekalert.org/pub_releases/2019-07/cwru-rdt072919.php [Accessed 2 Aug. 2019].