Human endogenous retrovirus (HERV) genomes are chromosomally integrated in all cells of an individual. They are normally transcriptionally silenced and transmitted only vertically. Enhanced expression of HERV-K accompanied by the emergence of anti-HERV-K-directed immune responses has been observed in
tumor patients and HIV-infected individuals. As HERV-K is usually not expressed and immunological tolerance development is unlikely, it is an appropriate target for the development of
immunotherapies. We generated a recombinant vaccinia virus (MVA-HKenv) expressing the HERV-K envelope
glycoprotein (ENV), based on the modified vaccinia virus Ankara (MVA), and established an animal model to test its vaccination efficacy. Murine
renal carcinoma cells (Renca) were genetically altered to express E. coli
beta-galactosidase (RLZ cells) or the HERV-K ENV gene (RLZ-HKenv cells).
Intravenous injection of RLZ-HKenv cells into syngenic BALB/c mice led to the formation of pulmonary
metastases, which were detectable by
X-gal staining. A single vaccination of
tumor-bearing mice with MVA-HKenv drastically reduced the number of pulmonary RLZ-HKenv
tumor nodules compared to vaccination with wild-type MVA. Prophylactic vaccination of mice with MVA-HKenv precluded the formation of RLZ-HKenv
tumor nodules, whereas wild-type MVA-vaccinated animals succumbed to
metastasis. Protection from
tumor formation correlated with enhanced HERV-K ENV-specific killing activity of splenocytes. These data demonstrate for the first time that HERV-K ENV is a useful target for
vaccine development and might offer new treatment opportunities for diverse types of
cancer.