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<p>Oncolytic viruses (OVs) can selectively infect and kill tumor cells. Although showing promise, several challenges impede OVs broad application in cancer therapy. A major obstacle is limited treatment duration due to preexisting or the induction of neutralizing immune responses toward the OVs following treatment. Widening the reservoir of OVs will allow replacement of treatment viruses following neutralization. This study aimed to identify new OVs and to test their oncolytic effect. Eight avian viruses (AVs) were tested for their ability to infect human and mice normal and cancerous cell lines. Viruses which displayed superior ability to selectively kill cancer cells <i>in vitro</i> were further tested for their ability to inhibit tumor growth 3 independent mice models. Three AVs induced cytopathic effects each inhibiting proliferation of at least 4 cancer cell lines tested; none affected normal fibroblasts. <i>In vivo</i>, growth of G361 melanoma cell tumors in nude mice was inhibited following intra-tumoral (i.t) injection of AVs. In two models of immunocompetent mice carrying tumors and injected i.t with AVs, tumors growth was significantly delayed. Albeit tumor growth commenced in correlation with the development of anti-virus antibody levels. These tested AVs together with their field-characterized variants, comprise a vast arsenal of potential OVs that may open the possibility of administration of several viruses in mix or in sequence to overcome both tumor resistance due to acquired mutations as well as neutralization by the rise of the acquired immune response. In conclusion, the AVs tested in this study demonstrated OVs characteristics and may be used to enable prolonged cancer virotherapy treatment.</p>

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Viruses of avian origin demonstrate potential for cancer virotherapy

  • 期刊论文

  • 发表日期：

    2026年2月21日

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  • Jacob Pitcovski,
  • Gilad Gallili,
  • Daria Oren Aharon,
  • Shir Malka,
  • Gal Yanovich,
  • Elad Milrot,
  • Ehud Shahar

摘要

Oncolytic viruses (OVs) can selectively infect and kill tumor cells. Although showing promise, several challenges impede OVs broad application in cancer therapy. A major obstacle is limited treatment duration due to preexisting or the induction of neutralizing immune responses toward the OVs following treatment. Widening the reservoir of OVs will allow replacement of treatment viruses following neutralization. This study aimed to identify new OVs and to test their oncolytic effect. Eight avian viruses (AVs) were tested for their ability to infect human and mice normal and cancerous cell lines. Viruses which displayed superior ability to selectively kill cancer cells in vitro were further tested for their ability to inhibit tumor growth 3 independent mice models. Three AVs induced cytopathic effects each inhibiting proliferation of at least 4 cancer cell lines tested; none affected normal fibroblasts. In vivo, growth of G361 melanoma cell tumors in nude mice was inhibited following intra-tumoral (i.t) injection of AVs. In two models of immunocompetent mice carrying tumors and injected i.t with AVs, tumors growth was significantly delayed. Albeit tumor growth commenced in correlation with the development of anti-virus antibody levels. These tested AVs together with their field-characterized variants, comprise a vast arsenal of potential OVs that may open the possibility of administration of several viruses in mix or in sequence to overcome both tumor resistance due to acquired mutations as well as neutralization by the rise of the acquired immune response. In conclusion, the AVs tested in this study demonstrated OVs characteristics and may be used to enable prolonged cancer virotherapy treatment.