Yale Cancer Center (YCC) researchers were awarded a $3.8 million grant from the National Cancer Institute to develop a new cytokine-based immunotherapy for melanoma. The scientists’ and their laboratories will collaborate to perform advanced preclinical testing and characterization of their drug to enable first-in-patient clinical trials as early as 2021.
Cytokines are powerful hormone-like molecules of the immune system and were among the first cancer immunotherapies to produce long-lasting responses in patients with late-stage cancer. Despite their promise, cytokine therapies have been hampered by severe immune-related toxicities and only limited anti-tumor effectiveness.
Marcus Bosenberg, M.D., Ph.D., interim director of the Yale Center for Immuno-Oncology (YCIO) and professor of Dermatology, Pathology, and Immunobiology, along with Aaron Ring, M.D., Ph.D., assistant professor of Immunobiology and Pharmacology at YCC, will lead the cytokine research. “This grant reflects the type of translational research that we aim to feature in the YCIO, moving innovative discoveries made in our laboratories into tangible therapies for patients,” said Bosenberg.
In addition to research funding, the award will establish Bosenberg and Ring as members of the Immuno-Oncology Translational Network (IOTN), a science network established by the Cancer Moonshot Initiative devoted exclusively to discovering and evaluating novel immune-based approaches to treat and prevent adult cancers.
Ring has focused his laboratory’s research on engineering cytokines to overcome their intrinsic limitations. “We can’t accept ‘nature’s solution’ to cytokine therapies, we need to tailor their properties to maximize their potential as drugs,” Ring added.
Using a technique called directed evolution, Ring and his team have screened hundreds of millions of variants of the cytokine interleukin-18 (IL-18) for improved versions that could retain strong activity deep within the tumor microenvironment. With seed funding from the Blavatnik Fund for Innovation at Yale, Ring’s lab succeeded in creating a therapeutic drug candidate called “decoy-resistant IL-18,” or DR-18. They then teamed-up with Bosenberg and his lab to evaluate the therapeutic potential DR-18 in cutting-edge mouse melanoma tumor models that his lab developed. “The remarkable activity of DR-18 in these models indicates that there is a lot of interesting biology surrounding IL-18 to investigate and exploit. Our collaboration, supported by the Yale Center for Precision Cancer Modeling, will enable a multidisciplinary effort to move these discoveries forward,” remarked Ring.