Biomedical Sciences ETDs
Publication Date
Fall 12-15-2024
Abstract
Tumor Necrosis Factor Alpha (TNF) can lead to tumor regression through its direct cytolytic activity, yet it has also been implicated to facilitate tumor progression. This scenario complicates the efficacy and applicability of TNF based therapeutics as treatment for malignancies. In the context of oncolytic virotherapy (OV) which uses replicating viruses to treat tumors and acts by triggering production of pro-inflammatory cytokines, exploring such mechanisms is vital. Here we show that a Myxoma based oncolytic virus (vPD1/IL12) can induce large amounts TNF. The presence of TNF in the context of vPD1/IL12 plays a detrimental role both for tumor regression by preventing establishment of anti-tumor immunity and inducing toxicities. Both phenomena can be alleviated by targeting certain forms of TNF using FDA approved TNF blockers. These data suggest that some aspects of OV-induced inflammation might represent a double-edged sword during therapy and that specific blockade of TNF might enhance the efficacy of these treatments.
Keywords
TNF, Immunotherapy, Myxoma, Oncolytic Virotherapy, OV, MYXV
Document Type
Dissertation
Language
English
Degree Name
Biomedical Sciences
Level of Degree
Doctoral
Department Name
Biomedical Sciences Graduate Program
First Committee Member (Chair)
Dr. Eliseo Castillo
Second Committee Member
Dr. Eric Bartee
Third Committee Member
Dr. Michelle Ozbun
Fourth Committee Member
Dr. Steven Bradfute
Fifth Committee Member
Dr. Chrystal Paulos
Recommended Citation
Valenzuela Cardenas, Miriam B.. "TNF PREVENTS ESTABLISHMENT OF ANTI-TUMOR IMMUNITY AND ELUCIDATES TOXICITIES FOLLOWING MYXOMA VIRUS BASED ONCOLYTIC VIROTHERAPY." (2024). https://digitalrepository.unm.edu/biom_etds/275
