Successful immunotherapy of an intraocular tumor in mice

Immune privilege in the eye is considered essential in the protection again st local sight-threatening inflammatory responses, However, the deviant imm une responses in the eye may also provide an ideal opportunity to uncontrol led growth of viruses or tumors by inhibiting intraocular immunological att ack. To establish to what extent immune privilege interferes with T cell-me diated antitumor immunotherapy, me established a new ocular tumor model in the mouse and tested whether well-defined tumor-specific CTLs can eradicate an immunogenic Intraocularly growing tumor, Tumor cells, transformed by hu man adenovirus type 5 early region 1 (Ad5E1), injected s.c. in a dose of 10 (7) cells, did not induce s.c. tumor growth in C57BL/6 mice, However, an in jection of 0.3 x 10(6) of these cells into the anterior chamber of the eye led to intraocular tumor growth in 95% of mice (n = 20), Tumor growth in th e eye did not induce systemic tumor-specific tolerance, because 70% of the mice were able to eradicate the tumor spontaneously after 5 weeks, Mice vac cinated s.c. with irradiated tumor cells were protected against intraocular tumor challenge, indicating that preactivated memory T cells are able to p rotect against intraocular tumor growth, Moreover, an i.v. injection of an Ad5E1-specific CTL clone was able to eradicate established intraocular AdSE 1-transformed tumors, whereas the anatomy of the eye remained intact, These results demonstrate that tumor-specific, CTL-mediated immunity can be used successfully fur the prevention and eradication of tumors growing in the i mmune-privileged anterior chamber of the eye, without detectable destructio n of the eye.