We are living in a golden era of oncology innovation. Advances in our understanding of biomarkers and immunotherapy applications are helping to radically redefine what is possible for patients; however, for all of the advancements, many of these technologies are only useful for a small subset of people. As we look to the next wave of precision medicine, researchers must explore mechanisms for expanding the impact of these technologies to larger patient populations.

Recent advancements in antibody-drug conjugate (ADC) technologies serve as an excellent example. ADC studies have shown tremendous efficacy in the treatment of tumors expressing a specific set of biomarkers; however, not all patients express the biomarkers necessary to reap the benefits of these breakthrough therapeutics.

But what if another type of drug conjugate, based on more common molecular interactions, could offer comparable, or even superior, tumor-targeting capabilities?

Within nature, sugar chains, known as glycans, are key components of all biological systems.ⁱ Within an organism, these sugars work to control and define fundamental biological processes. As a result, these natural sugars are also involved when those processes malfunction, contributing to a range of human diseases, including cancer.ⁱⁱ

Functionally, sugars impact a wide range of cancer biology, including cell proliferation, metabolism, adhesion, and signaling. These biological processes are at the heart of cancer hallmarks such as invasion, metastasis, and escaping the body’s immune surveillance system.^{ii, iii, iv}

Given the critical role of sugars in tumor biology, we are working to understand how these same sugars could be leveraged to improve clinical outcomes for patients. Once understood, these data points could provide novel targets for more selective and effective cancer therapies.

At Double Rainbow, our goal is to leverage the critical role of sugars in human biology to pioneer a new class of glyco-drug conjugate (GDC) technology to deliver the next generation of precision medicines. GDCs are a novel drug delivery approach using proprietary sugar motifs to deliver therapeutic payloads directly to diseased tissue.

Our sugar motifs work as molecular global positioning systems (GPS) to locate targeted cells and deliver a broad range of therapeutic agents. We believe that GDCs will allow new and existing medicines to link with our proprietary sugar motifs to exert enhanced therapeutic functions through specific interactions with sugar transporters or immunomodulatory sugar receptors.

As our team continues to push the limits of our technologies, we believe the advancement of our PRISM platform could allow our GDCs to target new regulators for immuno-oncology and improve drug delivery throughout the body – even in traditionally hard-to-target areas like the brain. By targeting immunomodulatory sugar receptors we hope to create avenues to undermine a cancer cell’s ability to escape immune surveillance and open it to the full effects of cancer immunotherapies.

It will take bold, new ideas to meaningfully improve survival and quality of life for people living with cancer. That is a key reason we at Double Rainbow are focused on developing revolutionary platform technologies that can help deliver a new era of medicine for patients around the world.

ⁱ A. Varki, R.D. Cummings, J.D. Esko, P. Stanley, G.W. Hart, M. Aebi, A.G. Darvill, T. Kinoshita, N.H. Packer, and J.H. Prestegard, et al., eds. (2015). Essentials of Glycobiology (Cold Spring Harbor Laboratory Press).
ⁱⁱ Pinho, S.S., and Reis, C.A. (2015). Glycosylation in cancer: mechanisms and clinical implications. Nat. Rev. Cancer 15, 540 – 555.
ⁱⁱⁱ Lau, K.S., Partridge, E.A., Grigorian, A., Silvescu, C.I., Reinhold, V.N., Demetriou, M., and Dennis, J.W. (2007). Complex N‑glycan number and degree of branching cooperate to regulate cell proliferation and differentiation. Cell 129, 123 – 134.
^iv Rodriguez, E., Schetters, S.T.T., and van Kooyk, Y. (2018). The tumor glycocode as a novel immune checkpoint for immunotherapy. Nat. Rev. Immunol. 18, 204 – 211.