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Developing and Evaluating Recombinant Immunotoxins against Latent Epstein Barr Virus Infected Cells
Author(s) -
Zhu Yuyi,
Weldon John
Publication year - 2020
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.2020.34.s1.05003
Subject(s) - immunotoxin , pseudomonas exotoxin , virus , virology , antibody , immunology , epstein–barr virus , oncolytic virus , fusion protein , medicine , biology , cancer research , recombinant dna , monoclonal antibody , gene , biochemistry
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. Individuals with healthy immune system can manage acute infections with minimal symptoms, but EBV often 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, yet there are currently no targeted treatments against latent EBV induced cancers. A potential treatment for both latent EBV infections and EBV‐induced malignancies is recombinant immunotoxins (RITs) targeted to the virus‐specific membrane protein, LMP1. 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 received FDA approval for the treatment of Hairy Cell Leukemia. Using a previously developed anti‐LMP1 antibody, we have cloned, expressed, and purified two anti‐LMP1 single‐chain variable fragment antibody joined recombinantly to either PE24 or PE38. We have begun to develop a HEK293 cell line that expresses LMP1 in order to evaluate the cytotoxicity of our anti‐LMP1 RITs. Subsequent experiments will evaluate these RITs as a therapeutic against EBV‐infected cell lines. Support or Funding Information This project was support by the Towson University’s Graduate Student Association and the Fisher College of Science and Mathematics