RESUMO
Recently, major advances have been made in the identification of antigens from human melanoma which are recognized by T cells. In spite of this, little is known about the optimal ways to use these antigens to treat patients with cancer. Progress in this area is likely to require accurate preclinical animal models, but the availability of such models has lagged behind developments in human tumor immunology. Whereas many of the identified human melanoma antigens are normal tissue differentiation proteins, analogous murine tumor antigens have not yet been identified. In this paper we identify a normal tissue differentiation antigen, tyrosinase-related protein 2 (TRP-2), expressed by the murine B16 melanoma which was found by screening a cDNA library from B16 with tumor-reactive cytotoxic T lymphocytes (CTL). A peptide conforming to the predicted MHC class I H2-Kb binding motif, TRP-2181-188, was identified as the major reactive epitope within TRP-2 recognized by these anti-B16 CTLs. By site-directed mutagenesis, it was shown that alteration of this epitope eliminated recognition of TRP-2. It was further demonstrated that a CTL line raised from splenocytes by repeated stimulation in vitro with this peptide could recognize B16 tumor and was therapeutic against 3-d-old established pulmonary metastases. The use of TRP-2 in a preclinical model of tumor immunotherapy may be helpful in suggesting optimal vaccination strategies for cancer therapy in patients.
Assuntos
Antígenos de Neoplasias/análise , Oxirredutases Intramoleculares , Isomerases/análise , Melanoma Experimental/imunologia , Animais , Sequência de Bases , Feminino , Isomerases/imunologia , Melanoma Experimental/terapia , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Relação Estrutura-Atividade , Linfócitos T/imunologia , Células Tumorais Cultivadas , VacinaçãoRESUMO
A benign tracheoesophageal fistula occurring as a complication of Barrett's ulcerative esophagitis is described. Surgical control of gastroesophageal reflux resulted in healing of the fistula, obviating the need for a resective procedure or esophageal exclusion. Although Barrett's ulcer has been reported as a cause of acquired esophagorespiratory fistula, to our knowledge, the important role of reflux control in the management of this difficult problem has not been discussed.
