Vaccination with recoverin, a cancer-associated retinopathy antigen, induces autoimmune retinal dysfunction and tumor cell regression in mice

Eur J Immunol. 2002 Aug;32(8):2300-7. doi: 10.1002/1521-4141(200208)32:8<2300::AID-IMMU2300>3.0.CO;2-7.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Abatacept
  • Animals
  • Antigens, CD
  • Antigens, Differentiation / physiology
  • Autoimmune Diseases / etiology*
  • CTLA-4 Antigen
  • Calcium-Binding Proteins / immunology*
  • Eye Proteins*
  • Female
  • Hippocalcin
  • Immunoconjugates*
  • Lipoproteins*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neoplasms, Experimental / therapy*
  • Nerve Tissue Proteins*
  • Paraneoplastic Syndromes / etiology
  • Recoverin
  • Retinal Diseases / etiology*
  • T-Lymphocytes, Cytotoxic / immunology
  • Vaccination


  • Antigens, CD
  • Antigens, Differentiation
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Calcium-Binding Proteins
  • Ctla4 protein, mouse
  • Eye Proteins
  • Immunoconjugates
  • Lipoproteins
  • Nerve Tissue Proteins
  • Rcvrn protein, mouse
  • Recoverin
  • Hippocalcin
  • Abatacept