An HSV-2 based oncolytic virus can function as an attractant to guide migration of adoptively transferred T cells to tumor sites

• Published in: Oncotarget Vol. 6; no. 2; pp. 902 - 914
• Main Authors: Fu, Xinping, Rivera, Armando, Tao, Lihua, Zhang, Xiaoliu
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 20.01.2015
• Subjects: Animals; Cell Line; Cell Line, Tumor; Cell Movement - immunology; Cercopithecus aethiops; Chemokines - immunology; Chemokines - metabolism; Combined Modality Therapy; Herpesvirus 2, Human - immunology; Herpesvirus 2, Human - physiology; Humans; Immunotherapy, Adoptive - methods; Interleukin Receptor Common gamma Subunit - deficiency; Interleukin Receptor Common gamma Subunit - genetics; Interleukin Receptor Common gamma Subunit - immunology; Mice, Inbred C57BL; Mice, Inbred NOD; Mice, Knockout; Mice, SCID; Mice, Transgenic; Neoplasms, Experimental - immunology; Neoplasms, Experimental - therapy; Neoplasms, Experimental - virology; Oncolytic Virotherapy - methods; Oncolytic Viruses - immunology; Oncolytic Viruses - physiology; Receptors, Chemokine - immunology; Receptors, Chemokine - metabolism; Research Paper; T-Lymphocytes - immunology; T-Lymphocytes - transplantation; Tumor Burden - immunology; Vero Cells
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.2817

Adoptive T-cell therapy has shown promises for cancer treatment. However, for treating solid tumors, there is a need for improving the ability of the adoptively transferred T cells to home to tumor sites. We explored the possibility of using an oncolytic virus derived from HSV-2, which can actively pull T effector cells to the site of infection, as a local attractant for migration of adoptively transferred T cells. Our data show that intratumoral administration of this virus can indeed attract active migration of the adoptively transferred T cells to the treated tumor. Moreover, once attracted to the tumor site by the virus, T cells persisted in there significantly longer than in mock-treated tumor. Chemokine profiling identified significant elevation of CXCL9 and CXCL10, as well as several other chemokines belonging to the inflammatory chemokine family in the virus-treated tumors. These chemokines initially guided the T-cell migration to and then maintained their persistence in the tumor site, leading to a significantly enhanced therapeutic effect. Our data suggests that this virotherapy may be combined with adoptive T-cell therapy to potentiate its therapeutic effect against solid tumors that are otherwise difficult to manage with the treatment alone.