With the lack of activity of the anti-KSHV RITs against the BCBL-1 cell line, we temporarily abandoned our collaborative efforts (with Dr. Larry Corey and Dr. Corey Caspar FHCRC, Seattle) to develop these agents as potential therapeutics. We began a new collaborative effort with Dr. Jens Kuhn of the NIAID Integrated Research Facility in Frederick, MD, to generate an RIT against the Ebola virus glycoprotein. This approach is headed by Dr. Yingyun Cai, a former postdoctoral fellow in the MSS, LVD who produced the RIT against KSHV gH, and subsequently joined Dr. Kuhn's group. At the IRF-Frederick, Dr. Cai designed an anti-Ebola RIT and visited MSS to express the protein in E. coli and purify it using standard methods for PE-based immunotoxins. With IRF-Frederick now approved to conduct BSL-4 research, the RIT will be tested against Ebola virus infection in cell culture. Promising results might suggest potential for this agent in the current Ebola outbreak. For KSHV, Dr. Corey's group has obtained evidence for strong lytic phase gene expression in KS tumors, a surprising finding given prevailing view that KS is more typically associated with latent phase of KSHV infection. Particularly high expression was noted for K8.1A and gH, raising enthusiasm for targeted cell killing for KSHV-associated syndromes (KS, PEL, MCD). Given the puzzling results with the anti-KSHV RITs, the FHCRC investigators have expressed high interest in testing the chimeric antigen receptor (CAR) approach against KSHV pathologies.
| Chatterjee, Deboeeta; Chandran, Bala; Berger, Edward A (2012) Selective killing of Kaposi's sarcoma-associated herpesvirus lytically infected cells with a recombinant immunotoxin targeting the viral gpK8.1A envelope glycoprotein. MAbs 4:233-42 |
| Cai, Yingyun; Berger, Edward A (2011) An immunotoxin targeting the gH glycoprotein of KSHV for selective killing of cells in the lytic phase of infection. Antiviral Res 90:143-50 |
