New Biomarkers May Serve as Companion Diagnostics for Patients Being Treated with IL-2

A transcriptional-profiling study has identified biomarkers related to efficacy of interleukin-2 (IL-2) treatment and has identified patient age as a key determining factor of clinical efficacy.

The study, conducted by Aelan Cell Technologies (San Francisco, CA, USA) and an international team of researchers from Wuhan University (Wuhan, China), Georgia Institute of Technology (Atlanta, GA, USA), Kazakh National Medical University (KazNMU; Almaty, Kazakhstan), the National Center for Cardiovascular Research (CNIC; Madrid, Spain), and PanAmerican Bioinformatics Institute (Santa Marta, Magdalena, Colombia), revealed patient age as a key determining factor in the efficacy of cell-based or pharmacological treatments. The study focused on the effect of age on the interaction of IL-2 treatments with human mesenchymal stem cells (MSCs). It was performed by modeling the aging of MSCs ex vivo, through the process of replicative senescence.

The findings highlight the possibility that in younger patients IL-2s and MSCs work in conjunction to fight cancer; whereas in older patients MSCs no longer work with the immune system and even provide cancerous tumors with a blood supply that aids in tumor invasiveness and metastasis.

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 possibility to much improve treatment decisions and cost savings. It has the potential to reshape how scientists and physicians look at outcomes of pharmacological interventions, particularly interleukin treatments.

“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,” said Victoria Lunyak, PhD, a principal investigator for the study and CEO and President of Aelan.

IL-2 is a potent cytokine, boosting the immune system in patients fighting various cancers. As human MSCs work like “internal pharmacies,” the interaction between these cells and IL-2 is critical. Chemicals produced by MSCs can prevent proliferation and promote differentiation of many inflammatory immune 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,” said co-first author Ping Niu, MD, PhD, associate chief physician, Wuhan University. 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,” said King Jordan, associate professor, Georgia Tech.

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,” said co-first author Aibek Smagul, KazNMU.

The study, by Niu P, et al., was published July 14, 2015, in the journal Oncotarget.

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