Nectin-1 is a marker of thyroid cancer sensitivity to herpes oncolytic therapy

Yu-Yao Huang1, Zhenkun Yu, Shu-Fu Lin

  • 1Head and Neck Service, C-1069, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.

Abstract

Insights

An oncolytic herpes virus, NV1023, effectively targets anaplastic, medullary, and papillary thyroid cancers, showing significant cytotoxicity. Nectin-1 expression is a key indicator for predicting patient response to this novel herpes oncolytic therapy.

Area of Science:

  • Oncolytic virotherapy
  • Thyroid cancer research
  • Molecular virology

Background:

  • Anaplastic thyroid cancer has a poor prognosis with limited treatment options.
  • Novel therapies are urgently needed for refractory thyroid cancers.

Purpose of the Study:

  • To evaluate an oncolytic herpes virus (NV1023) for its ability to infect and lyse human thyroid cancer cells.
  • To determine if herpes simplex virus receptor expression influences NV1023 efficacy.

Main Methods:

  • Assessed NV1023 entry and oncolysis in 12 human thyroid cancer cell lines.
  • Quantified herpes simplex virus receptor expression (nectin-1, herpes virus entry mediator) using flow cytometry.
  • Correlated receptor expression with viral entry and cancer cell lysis.

Main Results:

  • NV1023 demonstrated variable entry into thyroid cancer cells, strongly correlating with nectin-1 expression.
  • Nectin-1 transfections and blocking studies confirmed its critical role in viral entry.
  • Anaplastic, medullary, and papillary thyroid cancers showed >85% cytotoxicity after NV1023 exposure.
  • Follicular cancers were less sensitive to NV1023 oncolysis.

Conclusions:

  • NV1023 effectively induces significant cytotoxicity in anaplastic, medullary, and papillary thyroid cancers.
  • Nectin-1 serves as a novel biomarker for predicting thyroid cancer sensitivity to herpes oncolytic virotherapy.
  • Nectin-1 expression may guide patient selection for NV1023 therapy.

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