Immune Cell Modulation using Phosphodiesterase Activating Drug

Value Proposition

• Adjuvant to support the widespread use of immunotherapy in cancer.
• May improve the responses to checkpoint inhibitors (Keytruda) or CAR T cell activity.
• Diverse applications as a supplement to various precision cancer therapies.
• Repurposes a commercially available chemical compound for cancer treatment.
• Scalable synthesis, given the existing manufacturing infrastructure, facilitates commercialization.

Unmet Need

The use of PDE -modulation therapeutics has thus far been limited to PDE-inhibiting molecules. While there is preliminary evidence to suggest that PDE-activating therapies may benefit certain cancers, these treatments have not yet expanded beyond the benchtop. Furthermore, while immunotherapy has been a boon for oncologists, their patients, and pharmaceutical companies, unexpected failures of these drugs remain a persistent problem. There is therefore a need to best develop methods for implementing PDE-activating into the ever-growing world of cancer immunotherapies to improve patient outcomes and expand the applicability of immunotherapies into more diverse cancer types.

Technology Description

The disclosed technology embodies the application of an existing chemical compound into an adjuvant chemotherapy that upregulates immune activity. The compound activates PDE4, a phosphodiesterase that regulates various cell signaling pathways involved in immune activation. Thus far, the researchers have demonstrated that administration of the drug alone increases anti-cancer immune cell activity and prolongs survival in animal cancer models. This compound may be used to enhance the efficacy of existing and future immunotherapies, such as checkpoint blockades and CAR T cells. 

Stage of Development

• Preclinical: In vitro trials have been completed, demonstrating preliminary proof of concept and applicability to other diseases born from chronically elevated cAMP levels, such as ADPCKD. In vivo mouse studies have been completed and demonstrate an ability to increase immune activity and prolong survival.

Data Availability: Data available upon request.

Publication:

1. Hansen, Landon J., and Christopher M. Jackson. "The glioma microenvironment and its impact on antitumor immunity." Neuro-Oncology Advances 7.Supplement_4 (2025): iv19-iv31.