A Target and Screening System for the Identification of therapeutic candidates against secondary viral infections in cancer and immunocompromised diseaes

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A target and screening system for the identification of therapeutic candidates against secondary viral infections in cancer and immunocompromised diseases

Docket # 12-2771

Researchers in the molecular biology department at Princeton University, together with researchers in the department of microbiology and immunology, School of Medicine, University of Nevada, Reno have developed a unique monocycle screening system which will allow for the large scale monocyte culture for biochemical studies or high throughput screening for therapeutics.  As a particular example this system has been developed and demonstrated as a model for studying human cytomegalovirus reactivation.

In collaboration with the University of Nevada, Reno a viral protein, LUNA has been identified which regulates the ability of human cytomegalovirus to reactivate from a dormant state. The LUNA protein plays a role in the switch from dormant infection to reactivation. By blocking LUNA, the virus would be prevented from undergoing reactivation. Therapeutics against LUNA would be able to prevent reactivation of virus in immunocompromised hosts and therefore effectively prevent the development of life threatening disease for those suffering from cancer, AIDS or during organ transplantation. Additionally by preventing the reactivation of CMV from its dormant state, no active replication would take place thus limiting the risk of developing a drug-resistant mutant.

Nature of potential commercial application

Most antivirals target the active replicating state. For CMV, three anti-viral therapies targeting the active state are used, Valganciclovir, Ganciclovir and Foscarnet. However, these therapeutic approaches still carry a significant risk of developing drug-resistant virus strains, in addition to their toxic burden. Gancyclovir resistance, for example, occurs in up to 10% of lungs transplant recipients. The reality is that HCMV drug resistance is on the rise and the current regime of anti-viral drugs is ill equipped to handle this increasing burden. Without the development of better anti-CMV therapies, CMV will only continue to negatively impact the long-term quality of life of all immunocompromised patients.

 Since LUNA targeted therapeutics are less likely to develop resistance they could quickly out compete current CMV anti-virals.  It is also possible that anti-LUNA therapeutics could be used in combination with other CMV anti-virals to prevent resistance development as they have done with HIV anti-virals.  Either way, anti-LUNA drugs would be able to command a significant share of the $300 million per year CMV anti-viral market. 

A second avenue for commercial development is the monocyte suspension system itself.  Since monocytes can be infected by a number of different pathogens this  system can be adapted and used as a screen against a large number of diseases, which currently lack effective therapeutics.  Following our success with LUNA, the monocyte suspension system can serve as the launching pad for a company focused on developing therapeutics for the treatment of diseases of inflammatory and infectious origin. In order to surmount present obstacles to therapeutic development, we developed a method for maintaining freshly isolated human monocytes in the laboratory in a state similar to their status in the blood stream. These cells can be cultured in this state for up to 30 days post isolation. The suspension system is flexible enough to allow for large-scale culture for biochemical studies or high-throughput screening for therapeutics. As mentioned above the monocyte suspension system has been validated as a model for studying HCMV reactivation. 


·         Identification of new anti-virals for secondary infections related to cancer, transplant and immunocompromised patients

·         Identification of new therapeutic candidates for inflammatory diseases

·          Screening system offers a potential launching pad for startup focused on new therapeutic development



·         Use of stable monocytes ¿In vitro¿ for high-throughput screening

·         Provides a high-throughput screening method for evaluating monocyte secretion, migration and differentiation outcomes.

·         Provides a comprehensive solution for screening therapeutics  against all identified monocyte functions



Basic research continually highlights the roles the immune response plays as both a cause and regulator of cancer. Additionally, current cancer treatments weaken immune function leading to secondary infections, which often prove fatal. However, translating this information into new therapeutic directions has been limited by the ability to reduce such complex system responses into testable in vitro models. A prominent experimental roadblock is the monocyte. Monocytes, an important white blood cell population, are quintessential for the control of bacterial, viral, and parasitic infection. However, monocytes can also become infected by a number of pathogens, thus short-circuiting the immune response to an infection. In addition, over-stimulation of monocytes can lead to chronic inflammation contributing to the development of inflammatory diseases such as rheumatoid arthritis, multiple sclerosis, and atherosclerosis. Until recently, the study of human monocytes has been hindered by the inability to maintain the cells outside the body without their immediate differentiation into other cell types.



Hargett D., Shenk T., Experimental human cytomegalovirus latency in CD14+  monocytes, PNAS, November 16, 2010, Vol 107., No. 46, pg 20039-20044.

Lisa R. Keyes, Soland M, Hargett D., Bego MG., Rossetto CC, Almeida-Porada G., and St. Jeor S., HCMV protein LUNA is required for viral reactivation from latently infected primary CD14+ cells.  PLOS ONE, 2012, Pending publication.



Danna Hargett is a research fellow in the department of Molecular Biology at Princeton University.  Her research interests are in the pathogenesis of viruses that interact directly with immune cells, such as human cytomegalovirus and understanding how these infections contribute to the chronic inflammatory process.


Stephen St Jeor is a professor at the School of Medicine, department of microbiology and immunology, University of Nevada, Reno. His laboratory is interested in the pathogenesis of virus diseases. In the overall area of virus pathogenesis we are interested in the regulation of human cytomegalovirus latency and the pathogenesis of New World Hantaviruses.


Intellectual property and technology status:

Patent pending

Industrial collaborators or entrepreneurs are sought for the further development and commercialization of this technology.




Laurie Tzodikov

Princeton University Office of Technology Licensing ¿ (609) 258-7256¿ tzodikov@princeton.edu




Patent Information:
For Information, Contact:
Laurie Tzodikov
Licensing Associates
Princeton University
Danna Hargett
Stephen St. Jeor
Lisa Keyes
Mariana Bego
drug target
human cytomegalovirus