Successful immunotherapy of an intraocular tumor in mice
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Successful immunotherapy of an intraocular tumor in mice. / Schurmans, L R; den Boer, A T; Diehl, L; van der Voort, E I; Kast, W M; Melief, C J; Toes, R E; Jager, M J.
In: CANCER RES, Vol. 59, No. 20, 15.10.1999, p. 5250-4.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Successful immunotherapy of an intraocular tumor in mice
AU - Schurmans, L R
AU - den Boer, A T
AU - Diehl, L
AU - van der Voort, E I
AU - Kast, W M
AU - Melief, C J
AU - Toes, R E
AU - Jager, M J
PY - 1999/10/15
Y1 - 1999/10/15
N2 - Immune privilege in the eye is considered essential in the protection against local sight-threatening inflammatory responses. However, the deviant immune responses in the eye may also provide an ideal opportunity to uncontrolled growth of viruses or tumors by inhibiting intraocular immunological attack. To establish to what extent immune privilege interferes with T cell-mediated antitumor immunotherapy, we 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 human 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 injection 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 the eye did not induce systemic tumor-specific tolerance, because 70% of the mice were able to eradicate the tumor spontaneously after 5 weeks. Mice vaccinated s.c. with irradiated tumor cells were protected against intraocular tumor challenge, indicating that preactivated memory T cells are able to protect against intraocular tumor growth. Moreover, an i.v. injection of an Ad5E1-specific CTL clone was able to eradicate established intraocular Ad5E1-transformed tumors, whereas the anatomy of the eye remained intact. These results demonstrate that tumor-specific, CTL-mediated immunity can be used successfully for the prevention and eradication of tumors growing in the immune-privileged anterior chamber of the eye, without detectable destruction of the eye.
AB - Immune privilege in the eye is considered essential in the protection against local sight-threatening inflammatory responses. However, the deviant immune responses in the eye may also provide an ideal opportunity to uncontrolled growth of viruses or tumors by inhibiting intraocular immunological attack. To establish to what extent immune privilege interferes with T cell-mediated antitumor immunotherapy, we 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 human 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 injection 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 the eye did not induce systemic tumor-specific tolerance, because 70% of the mice were able to eradicate the tumor spontaneously after 5 weeks. Mice vaccinated s.c. with irradiated tumor cells were protected against intraocular tumor challenge, indicating that preactivated memory T cells are able to protect against intraocular tumor growth. Moreover, an i.v. injection of an Ad5E1-specific CTL clone was able to eradicate established intraocular Ad5E1-transformed tumors, whereas the anatomy of the eye remained intact. These results demonstrate that tumor-specific, CTL-mediated immunity can be used successfully for the prevention and eradication of tumors growing in the immune-privileged anterior chamber of the eye, without detectable destruction of the eye.
KW - Adenoviruses, Human
KW - Animals
KW - Anterior Chamber
KW - Eye Neoplasms
KW - Immunization
KW - Immunotherapy, Adoptive
KW - Male
KW - Mice
KW - Mice, Inbred C57BL
KW - T-Lymphocytes, Cytotoxic
M3 - SCORING: Journal article
C2 - 10537305
VL - 59
SP - 5250
EP - 5254
JO - CANCER RES
JF - CANCER RES
SN - 0008-5472
IS - 20
ER -