Article abstract
Nature Medicine 14, 37 - 44 (2008)
Published online: 9 December 2007 | doi:10.1038/nm1681
Purging metastases in lymphoid organs using a combination of antigen-nonspecific adoptive T cell therapy, oncolytic virotherapy and immunotherapy
Jian Qiao1, Timothy Kottke1, Candice Willmon1, Feorillo Galivo1, Phonphimon Wongthida1, Rosa Maria Diaz1, Jill Thompson1, Pamela Ryno1, Glen N Barber2, John Chester3, Peter Selby3, Kevin Harrington4, Alan Melcher3,6 & Richard G Vile1,3,5,6
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.
- Molecular Medicine Program, Mayo Clinic, Rochester, Minnesota 55905, USA.
- Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, Florida 33136, USA.
- Cancer Research UK Clinical Centre, Leeds Teaching Hospitals UK National Health Service Trust and Leeds Institute of Molecular Medicine, University of Leeds, Leeds LS9 7TF, UK.
- The Institute of Cancer Research, London SW7 3RP, UK.
- Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905, USA.
- These authors contributed equally to this work.
Correspondence to: Richard G Vile1,3,5,6 e-mail: vile.richard@mayo.edu
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