Immunotherapy can reject intracranial tumor cells without damaging the brain despite sharing the target antigen.
Although vaccines targeting tissue differentiation Ags represent a promising strategy for cancer immunotherapy, the risk of triggering autoimmune damage to normal tissues remains to be determined. Immunizing against a melanoma-associated Ag, dopachrome tautomerase (DCT), which normal melanocytes and glial cells also express, allowed concurrent analysis of autoimmune consequences in multiple tissues. We show that vaccination with recombinant adenovirus expressing DCT elicited a strong CTL response in C57BL/6 mice, leading to protection against intracranial challenge with B16-F10 melanoma cells. Both histological analysis and behavioral testing indicated that there was no evidence of neuropathology in vaccinated animals and long-term survivors. Although vitiligo or demyelination could be induced by additional stimuli (i.e., surgery or inflammation) in DCT-vaccinated mice, it did not extend beyond the inflammatory area, suggesting that there is self-regulatory negative feedback in normal tissues. These results demonstrate that it is possible to vaccinate against a tumor embedded in a vital organ that shares the target Ag.
Bridle
Byram W
BW
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Li
Jian
J
Jiang
Shucui
S
Chang
Ruby
R
Lichty
Brian D
BD
Bramson
Jonathan L
JL
Wan
Yonghong
Y
D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D001932:Brain Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D005260:Female; D018390:Gene Targeting / Q000379:methods; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D007276:Injections, Intraventricular; D019746:Intramolecular Oxidoreductases / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D014820:Vitiligo / Q000276:immunology / Q000473:pathology / Q000517:prevention & control
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase