Purging metastases in lymphoid organs using a combination of antigen-nonspecific adoptive T cell therapy, oncolytic virotherapy and immunotherapy

Jian Qiao, Timothy Kottke, Candice Willmon, Feorillo Galivo, Phonphimon Wongthida, Rosa Maria Diaz, Jill Thompson, Pamela Ryno, Glen N. Barber, John Chester, Peter Selby, Kevin Harrington, Alan Melcher, Richard G. Vile

Research output: Contribution to journalArticlepeer-review

127 Scopus citations

Abstract

In many common cancers, dissemination of secondary tumors via the lymph nodes poses the most significant threat to the affected individual. Metastatic cells often reach the lymph nodes by mimicking the molecular mechanisms used by hematopoietic cells to traffic to peripheral lymphoid organs. Therefore, we exploited naive T cell trafficking in order to chaperone an oncolytic virus to lymphoid organs harboring metastatic cells. Metastatic burden was initially reduced by viral oncolysis and was then eradicated, as tumor cell killing in the lymph node and spleen generated protective antitumor immunity. Lymph node purging of tumor cells was possible even in virus-immune mice. Adoptive transfer of normal T cells loaded with oncolytic virus into individuals with cancer would be technically easy to implement both to reduce the distribution of metastases and to vaccinate the affected individual in situ against micrometastatic disease. As such, this adoptive transfer could have a great therapeutic impact, in the adjuvant setting, on many different cancer types.

Original languageEnglish (US)
Pages (from-to)37-44
Number of pages8
JournalNature medicine
Volume14
Issue number1
DOIs
StatePublished - Jan 2008

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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