Induction of tumor antigen-specific immunity in vivo by a novel vaccinia vector encoding safety-modified simian virus 40 T antigen

Background: Evidence that simian virus 40 (SV40) is associated with human m esotheliomas, osteosarcomas, and brain tumors suggests that a recombinant v accine directed against lethal cancers expressing SV40 T antigen (Tag) coul d have clinical utility, To address this potential need, we designed a nove l vaccinia virus construct that encodes an SV40 Tag in which oncogenic doma ins were excluded and immunogenic domains were preserved. We named this rec ombinant construct vaccinia-encoding safety-modified SV40 Tag (vac-mTag). M ethods: Purified vac-mTag was characterized by DNA sequencing, reverse tran scription-coupled polymerase chain reaction, western blot analysis, and imm unocytochemical techniques. Induction of Tag-specific immunity was examined by cytolytic T-cell assays, and the efficacy of vac-mTag in protecting ani mals against Tag-expressing tumors and in treating pre-established microsco pic tumors was evaluated in vac-mTag-immunized BALB/c mice. Results: The im mune response elicited by vac-mTag in C57BL/6 and BALB/c mice included an S V40 Tag-specific cytolytic T-lymphocyte activity against syngeneic (identic al genetic background) SV40 Tag-expressing tumor targets. Immunization of m ice with a single dose of vac-mTag resulted in potent protection against su bsequent challenge with a lethal mouse cancer expressing SV40 Tag. In addit ion, single-dose vac-mTag immunization coadministered with interleukin 2 pr oduced a possible therapeutic effect against a preadministered microscopic (but lethal) burden of Tag-expressing tumor cells in vivo. Conclusion: vac- mTag induces an effective immune response in mice that is specific for a tu mor-associated antigen. This response protects against a lethal tumor chall enge and results in a possible therapeutic effect against Tag-expressing tu mors in vivo. Thus, vac-mTag provides a new avenue for the development of t herapies for human cancers thought to be associated with SV40.