San Francisco, CA -Aelan Cell Technologies, with an international research team, today 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.
Other authors on the study include Lu Wang and Ying Sha from the School of Biology, Georgia Institute of Technology, Atlanta; Aliya Nussupbekova, Aday Amirbekov, Aiman Sadvakas and Akan A Akanov from Kazakh National Medical University, Almaty, Kazakhstan; and Laura Martín Pérez and Beatriz G. Gálvez from the Department of Cardiovascular Development and Repair, National Center for Cardiovascular Research (CNIC), Madrid.
The research was supported by grants from the Spanish Ministry of Science and Innovation (SAF 2010-15239), international FPI fellowships from the Spanish Ministry, grants from the Spanish Ministry's Ramon y Cajal Programme, the Bolashak International Scholarship and Kazakh National Medical University.
About Aelan Cell Technologies:
Aelan Cell Technologies is a San Francisco startup engaged in the research, discovery, development and commercialization of innovative biomedical technologies for the advancement of human health and longevity. With a growing intellectual property portfolio of disruptive technologies and medical tools, Aelan has assembled an experienced team -- bringing together scientific and business expertise -- to successfully lead its products through each phase of development.
About Wuhan University:
Wuhan University is a public research university in Wuhan, Hubei, China. It is one of China's most prestigious institutions, holding the top position in numerous national rankings and measures. Located near the Yangzi River, it is known as the most beautiful university in China. Areas of excellence range from biology and life sciences to engineering and humanities. Wuhan University also has an impressive international reputation and has established cooperative relationships with many universities and research institutes around the world. In 1999, the world-renowned journal "Science" listed Wuhan University as one of the most prominent institutions of higher education in China. In 2014, Wuhan University was listed by "The Times" as one of the top 400 universities in the world.
About Kazakh National Medical University:
Located in Almaty, Kazakhstan, Kazakh National Medical University (KazNMU) is the leading medical institute in the country. Many of Kazakhstan's most prominent physicians are affiliated with the university, which is dedicated to S.D. Asfendiyarov, who was the first rector for the university when it was established in 1931. More than 11,000 students study at KazNMU, and there are more than 1500 faculty members, including more than 200 doctors of science, 130 professors, over 500 candidates of science and 15 Laureates of State.