Synergistic antitumor effects of immune cell-viral biotherapy.
Targeted biological therapies hold tremendous potential for treatment of cancer, yet their use has been limited by constraints on delivery and effective tumor targeting. We combined an immune effector cell population [cytokine-induced killer (CIK) cells] with an oncolytic viral therapy to achieve directed delivery to, and regression of, tumors in both immunodeficient and immunocompetent mouse models. Preinfection of CIK cells with modified vaccinia virus resulted in a prolonged eclipse phase with the virus remaining hidden until interaction with the tumor. Whole-body imaging revealed that the cells retained their ability to traffic to and to infiltrate the tumor effectively before releasing the virus. These results illustrate the potential of combining biotherapeutics for synergistic effects that more effectively treat cancer.
Thorne
Steve H
SH
Departments of Pediatrics, Radiology, Microbiology, and Immunology Stanford University School of Medicine, Stanford, CA 94305, USA.
Negrin
Robert S
RS
Contag
Christopher H
CH
D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000821:virology; D008325:Mammary Neoplasms, Experimental / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000628:therapy*; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000628:therapy; D014183:Transplantation, Heterologous; D014616:Vaccinia virus / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication
D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; C098080:MICB antigen