Lead Inventor:
Yuan Chang, M.D.;
Patrick Moore, M.D., M.P.H.
Kaposi's sarcoma-associated herpesvirus gene (KSHV/HHV8) LANA2 is a novel therapeutic target in virally induced cancers in Castleman's disease and primary effusion lymphoma.
Kaposi's sarcoma-associated herpesvirus (KHSV) or human herpesvirus 8 (HHV8) is one of the few types of cancers that results from viral infection and can cause Castleman's disease and primary effusion lymphoma. These diseases are commonly found in HIV/AIDS patients due to a diminished immune system. Many of the current treatment options for these types of cancer rely on traditional cancer therapies such as chemotherapy or radiation, or on traditional antiviral therapies such as glancovir. While these treatments have shown marginal efficacy, no therapies that target this specific virus are in existence. This technology identifies the viral gene Latency associated nuclear antigen 2 (LANA2) and provides both the gene's sequence as well as the B-cell specific promoter that gives the gene specificity after infection. Moreover, sequencing of the gene has led to the isolation of monoclonal antibodies against LANA2, a reagent that could be used both in the lab as well as a diagnostic tool in the clinic.
Targeting LANA2 could allow the development of therapeutics that are able to act specifically on the virally derived tumors.
LANA2 was shown to interact with p53, one of the cell's main defenses against cancer. By inhibiting the action of p53, LANA2 is able to cause damaged cells to continue to divide rather than self-destruct, or undergo apoptosis. The interaction of p53 and LANA2 was demonstrated by co-transfecting human cells with p53 and LANA2 and observing a decrease in the amount of apoptosis. This interaction was further confirmed by treating cells with LANA2 and doxorubicin, a potent activator of p53-mediated apoptosis, and observing a decrease in apoptosis over controls. Together, these experiments provide strong evidence that LANA2 is a critical factor in the oncogenesis of KSHV/HHV8. Interfering with the interaction of p53 and LANA2 with small molecule-based therapies could lead to a decrease in the incidence of cancer of KSHV/HHV8 in Castleman's disease and primary effusion lymphoma.
Applications:
-- The interaction of LANA2 with p53 is a novel target for the development of therapeutics for the treatment of KSHV/HHV8-related cancers in Castleman's disease or primary effusion lymphoma.
-- Knowledge of the specific viral LANA2 gene sequence will allow development of RNAi and RNA antisense-based therapeutics.
-- Monoclonal antibodies could be used to identify the origin of tumors in the clinic or as a lab reagent.
-- B-cell specific promoter region can be used to direct gene expression to hematopoietic tissues in gene therapy.
-- Use of LANA2 sequence in transfection could immortalize primary cell cultures.
Advantages:
-- Targeting LANA2 specifically will cut down on the side effects associated with chemotherapy or other treatments that target rapidly dividing cells.
-- Targeting LANA2 specifically will also eliminate the need to use costly and unstable antiviral therapies. This will also help eliminate the resistance that viruses gain from prolonged exposure to antiviral agents.
-- LANA2-specific therapies could prove to be more effective than any current therapeutic regime as it targets the specific infection rather than the general process.
-- Monoclonal antibodies against LANA2 could more accurately detect KSHV/HHV8 infected cells than histology or other means of detection.
-- Virally derived B-cell specific promoter sequences could direct gene expression in gene therapy approaches without the concern of mammalian-promoter specific gene silencing.
Patent information: 6,653,465 ~ see link below.
Licensing Status: Available for licensing and sponsored research support
Related Publications:
C. Rivas, A. Thick, C. Parravicini, P. Moore, Y. Chang.
Kaposi's Sarcoma-Associated Herpesvirus LANA2 Is a B-Cell-Specific Latent Viral Protein that Inhibits p53. Journal of Virology, Vol. 75, Issue 1, Jan. 2001, pp. 429-438.