Aelan identified the age of patients as a key determining factor in the efficacy of IL-2 cancer treatments
Aelan Cell Technologies, with an international research team, have released a study that reveals that age is a key determining factor in the efficacy of cell-based or pharmacological treatments. The study, published in the advanced online publication of Oncotarget: Gerotarget (Focus on Aging) focused on the effect of age on the interaction of Interleukin-2 (IL-2) treatments with human mesenchymal stem cells (MSCs). The collaborative study was performed by modeling the aging of MSCs ex-vivo, through a process called replicative senescence.
The research highlights the possibility that in younger patients IL-2s and MSCs work in conjunction to fight cancer. However, in older populations, MSCs no longer work with the immune system and actually provide cancerous tumors with a blood supply that aids in the invasiveness and metastasis of the tumor. As cancer therapies are among the costliest and most toxic pharmacological treatments, the opportunities for more efficient and effective treatment presented by this new information offer the possibility of tremendous cost savings.
The new information found in this study has the potential to reshape the way scientists and physicians look at the outcomes of pharmacological interventions, particularly Interleukin treatments. IL-2, approved by the FDA and several European countries, is a potent cytokine that is known to boost the immune system in patients fighting cancers such as malignant melanoma, renal cell cancer, leukemias and lymphomas.
"Our study highlights the importance of age as a factor when designing cell-based or pharmacological therapies for older patients, and it predicts measurable biomarkers characteristic of an environment that is conducive to cancer cells' invasiveness and metastasis," says Victoria Lunyak, Ph.D., a principal investigator for the study and the CEO and President of Aelan. Because human MSCs work as 'internal pharmacies' the interaction between these cells and IL-2 is of utmost importance. Chemicals produced by MSCs can prevent proliferation and promote differentiation of many inflammatory immune cells, including T cells, natural killer cells, B cell, monocytes, macrophages and dendritic cells. With aging, the inventory in these MSCs can change because aging affects MSC-mediated cellular communication circuitry. "We have shown that the IL-2-triggered immunomodulatory capacity of MSCs could be severely affected by replicative aging," notes Ping Niu, MD, PhD, an associate chief physician at Wuhan University and the first author on the paper. In fact, genome-wide transcriptional profiling of MSCs from human patients exposed to therapeutic doses of IL-2 showed significant aging-related differences in the transcriptional programs in human stem cells.
"Our computational analysis of transcriptional data sets of MSC response to IL-2 revealed precisely which biological pathways and gene targets are activated in response to drug treatment, all of which could be prioritized for further experimental studies with in-vivo models and in clinical settings," says King Jordan, an associate professor at the Georgia Institute of Technology whose lab has used sophisticated computation algorithms to depict these changes. Aelan will continue to conduct research on these biological pathways and work toward the clinical trial stage.
This new study, along with previously published data, is another step toward explaining contradicting reports regarding the tumor-promoting or tumor-suppressing properties of MSCs observed in clinical applications.
"Our finding opens the door to development of new companion diagnostics to IL-2 treatment, which will help to select the right patients to undergo IL-2 treatments," says Aibek Smagul, a visiting scientist from the Genomic Center of Kazakh National Medical University (KazNMU) who worked closely with Dr. Lunyak's group on this discovery.