Lead investigator: Alexander Muller, PhD
Collaborators: Souvik Dey, PhD, and George Prendergast, PhD

Tumors must attract a blood supply to survive and grow. The neovascularization of tumors is characterized by an excessive and disorganized growth of blood vessels. During their pioneering work on the role of IDO enzymes in driving tumoral immune escape, LIMR scientists discovered that the IDO1 enzyme also contributes significantly to sustaining the aberrant blood vasculature of tumors.

Advancing from this finding, they defined a new use for IDO1 inhibitors when combined with drugs that can preferentially kill cells lacking nutrients (a common characteristic of solid tumors). This advance was important, because it opened many new uses for IDO1 inhibitors in combination drug therapy for cancer therapeutics, beyond improving anti-tumor immune responses, as previously known.

Technology description

LIMR’s technology encompasses new uses of IDO inhibitors to enhance the activity of anti-angiogenic or antimetabolic drugs used to treat cancer or in other disease settings where ablation of a pathogenic blood vasculature is desired. Because traditional treatment modalities, such as chemotherapy and radiation therapy, exhibit general toxicities, the therapeutic window is small, contributing to the lack of durable responses too often seen with such treatments. This proprietary combination treatment platform can leverage the potential of next-generation, stress-enhanced antitumor agents to improve therapeutic responses, while sparing normal tissues. In one embodiment, the technology illustrates how IDO inhibitors can be used to empower anti-angiogenic effects.

The new uses described do not rely upon the involvement of adaptive immune cells, thereby greatly expanding the number of therapeutic combinations and applications for IDO inhibitors, which would otherwise be non-obvious to practice.

Business opportunity

IDO inhibitors offer broad interest for cancer treatment, with preclinical and emerging clinical evidence that they can safely enhance the efficacy of chemotherapy, radiotherapy, radio-chemotherapy and immunotherapy. The present technology greatly expands the scope of uses of this drug class, including combinations with anti-angiogenic or hypoxia/metabolic stress targeted therapies in cancer and other diseases. As such, the technology is enabling for companies to enhance the reach of non-immunologically based modalities, and/or expand on opportunities to market owned IDO inhibitors with other owned modalities.

The large global market for cancer drugs is expected to increase from $85 billion in 2016 to $155.6 billion by 2025, according to the research and consulting firm Transparency Market Research.

Intellectual property position

New uses of IDO inhibitors in combination drug therapy: Patent pending.

Relevant publications

Mondal A, Smith C, DuHadaway JB, Sutanto-Ward E, Prendergast GC, Bravo-Nuevo A and Muller AJ. (2016). IDO1 is an integral mediator of inflammatory neovascularization. EBioMed 14: 74-82.

Smith C, Chang MY, Parker KH, Beury DW, DuHadaway JB, Flick HE, Boulden J, Sutanto-Ward E, Soler AP, Laury-Kleintop LD, Mandik-Nayak L, Metz R, Ostrand-Rosenberg S, Prendergast GC and Muller AJ. (2012). IDO is a nodal pathogenic driver of lung cancer and metastasis development. Cancer Discov 2: 722-35.