Vaccination with recoverin, a cancer-associated retinopathy antigen, induces autoimmune retinal dysfunction and tumor cell regression in mice.
Recoverin (Rec)-specific CTL present in peripheral blood recognize Rec-expressing tumor cells of patients with cancer-associated retinopathy (CAR), a paraneoplastic retinopathy syndrome. To evaluate the effects of Rec on retina and cancer cells, we generated an experimental mouse model, tested the induction of Rec-specific anti-tumor CTL, and analyzed retinal function using electroretinogram (ERG) in these animals. We observed a Rec-specific CTL response in BALB/c mice and significant growth inhibition of Rec-expressing syngeneic MethA fibrosarcoma cells in vivo. R64 (AYAQHVFRSF) peptide, derived from Rec that induces anti-tumor CTL in humans, produced anti-tumor effects in BALB/c mice. Furthermore, elevated anti-Rec antibodies correlated with decreased ERG amplitudes in Rec, Rec-expressing tumor and R64-treated mice. These data suggest that Rec contains amino acid sequences which cause retinal dysfunction, but they also induce anti-tumor CTL and tumor regression. These observations describe initial characterization of the CAR mouse model, a necessary step in developing new insight into immunological mechanisms of paraneoplastic syndromes and tumor immunity for potential immunotherapeutic approaches to cancer.
Maeda
Akiko
A
Department of Ophthalmology, University of Washington, Seattle, WA 98195-6485, USA.
Maeda
Tadao
T
Ohguro
Hiroshi
H
Palczewski
Krzysztof
K
Sato
Noriyuki
N
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000502:physiology; D001327:Autoimmune Diseases / Q000209:etiology*; D060908:CTLA-4 Antigen; D002135:Calcium-Binding Proteins / Q000276:immunology*; D005136:Eye Proteins; D005260:Female; D051597:Hippocalcin; D018796:Immunoconjugates; D008074:Lipoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000628:therapy*; D009419:Nerve Tissue Proteins; D010257:Paraneoplastic Syndromes / Q000209:etiology; D051603:Recoverin; D012164:Retinal Diseases / Q000209:etiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D002135:Calcium-Binding Proteins; C556707:Ctla4 protein, mouse; D005136:Eye Proteins; D018796:Immunoconjugates; D008074:Lipoproteins; D009419:Nerve Tissue Proteins; C496732:Rcvrn protein, mouse; D051603:Recoverin; D051597:Hippocalcin; D000069594:Abatacept