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Oncolytic Herpes Simplex Virus Therapy for the Treatment of Pediatric Rhabdomyosarcoma

Leddon, Jennifer
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1427980753

Abstract Details

2015, PhD, University of Cincinnati, Medicine: Immunology.
Multiple studies have indicated that in addition to direct oncolysis, virotherapy promotes an antitumor cytotoxic T cell response important for efficacy. To study this phenomenon further, we tested three syngeneic murine sarcoma models that displayed varied degrees of permissiveness to oncolytic herpes simplex virus replication and cytotoxicity in vitro, with the most permissive being comparable to some human sarcoma tumor lines. The in vivo antitumor effect ranged from no or modest response to complete tumor regression and protection from tumor re-challenge. The in vitro permissiveness to viral oncolysis was not predictive of the in vivo anti-tumor effect, which was T-cell mediated with a tumor-specific antigen response required for maximal anti-tumor activity. Further analysis of the innate and adaptive immune microenvironment revealed potential correlates of susceptibility and resistance, including favorable and unfavorable cytokine profiles, differential composition of intratumoral myeloid cells, and baseline differences in tumor cell immunogenicity and tumor-infiltrating T-cell subsets. These findings suggest that understanding the immunological mechanisms of tumor susceptibility and resistance will be necessary to fully leverage the antitumor effects of this therapeutic platform.
Tim Cripe, M.D. Ph.D. (Committee Chair)
Rhonda Cardin, Ph.D. (Committee Member)
Balveen Kaur, Ph.D. (Committee Member)
George Deepe, M.D. (Committee Member)
David Hildeman, Ph.D. (Committee Member)
Michael Jordan, M.D. (Committee Member)
152 p.
Immunology
sarcoma; immunotherapy; oncolytic; virotherapy; HSV

Recommended Citations

Citations

  • Leddon, J. (2015). Oncolytic Herpes Simplex Virus Therapy for the Treatment of Pediatric Rhabdomyosarcoma [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1427980753

    APA Style (7th edition)

  • Leddon, Jennifer. Oncolytic Herpes Simplex Virus Therapy for the Treatment of Pediatric Rhabdomyosarcoma. 2015. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1427980753.

    MLA Style (8th edition)

  • Leddon, Jennifer. "Oncolytic Herpes Simplex Virus Therapy for the Treatment of Pediatric Rhabdomyosarcoma." Doctoral dissertation, University of Cincinnati, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1427980753

    Chicago Manual of Style (17th edition)

ucin1427980753
982
© 2015, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.