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Recombinant Immunotoxins against Latent Epstein Barr Virus Infections
Author(s) -
Zhu Yuyi,
Emmanuel Muhsinat,
Weldon John E.
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.793.7
Subject(s) - immunotoxin , virus , virology , antibody , pseudomonas exotoxin , epstein–barr virus , immunology , fusion protein , biology , population , medicine , recombinant dna , monoclonal antibody , gene , biochemistry , environmental health
Epstein Barr virus (EBV), commonly associated with acute infectious mononucleosis, is an oncogenic virus implicated in thousands of cancer‐related deaths every year worldwide. Estimates suggest that 90–95% of the population worldwide are infected with EBV, but acute infections are controlled with minimal symptoms by a healthy immune system. Like all herpesviruses, however, EBV persists in a latent state even after the acute infection has cleared. Studies have shown a definitive link between latent EBV infections and the development of certain cancers such as nasopharyngeal cancer and Burkitt's lymphoma, but there are currently no treatments for latent infections. A potential treatment for both latent EBV infections and EBV‐induced malignancies is antibody therapy targeted to virus‐specific membrane proteins. We have identified two EBV‐specific membrane proteins expressed on infected cells, LMP1 and LMP2, and are developing HEK293 cell lines constitutively expressing each of these proteins. We plan to develop recombinant immunotoxins (RITs) targeted to each of these proteins. RITs are fusion proteins comprised of an antibody and protein toxin designed to identify and kill specific populations of cells. RITs using the bacterial toxin Pseudomonas exotoxin A (PE) have been extensively studied. Several RITs are in clinical trials, and one (moxetumomab pasudotox) has recently received FDA approval for the treatment of Hairy Cell Leukemia. Using a previously developed anti‐LMP1 antibody, we have begun work to clone, express, and purify an anti‐LMP1 single‐chain variable fragment antibody joined recombinantly to a cytotoxic fragment of PE. We plan to evaluate this and other RITs as potential therapeutics for EBV‐related malignancies. Support or Funding Information This project was supported by the Towson University's Fisher College of Science and Mathematics. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .