RESUMEN
Neoplastic cells are believed to evade the immune system due, in part, to their inability to successfully provide a secondary, costimulatory signal for a T lymphocyte proliferative response. This report describes the generation and investigation of genetically engineered canine mammary tumor (CMT) cells that express canine B7-1, canine B7-2, or human B7-2. These transfected cells were used as stimulators in an allogeneic, costimulation assay. CMT cells transfected with canine B7-1 induced the greatest proliferation (7-fold increase), followed by CMT cells transfected with canine B7-2 (5-fold increase). The specificity of the canine B7-2 stimulatory response was demonstrated by a 38% reduction in proliferation caused by an anti-canine B7-2 blocking antibody. These results suggest that canine mammary tumor cells transfected with canine B7-1 or canine B7-2 may be useful for immunotherapeutic purposes.
Asunto(s)
Antígenos CD/inmunología , Antígeno B7-1/inmunología , Leucocitos Mononucleares/inmunología , Neoplasias Mamarias Experimentales/inmunología , Glicoproteínas de Membrana/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/farmacología , Antígenos CD/genética , Antígeno B7-1/genética , Antígeno B7-2 , Células Clonales , Perros , Femenino , Humanos , Inmunoterapia Activa/métodos , Interferón gamma/inmunología , Interferón gamma/farmacología , Activación de Linfocitos/inmunología , Masculino , Neoplasias Mamarias Experimentales/genética , Neoplasias Mamarias Experimentales/metabolismo , Glicoproteínas de Membrana/antagonistas & inhibidores , Glicoproteínas de Membrana/genética , Proteínas Recombinantes , Linfocitos T/inmunología , Transfección/métodosRESUMEN
This study was conducted to distinguish canine perianal gland carcinomas from adenomas using monoclonal antibodies (MAbs). The adenomas generally retain the lobular architecture, but some may contain focal areas of cellular pleomorphism. These changes may suggest malignant transformation and have led to discordant interpretations. To address this histopathological confusion, two perianal gland carcinoma-associated antigens were defined by mouse MAbs 4A9 and 1A10. These MAbs, generated against a canine mammary carcinoma cell line, reacted strongly with perianal gland carcinoma in preliminary screening and therefore were selected for further investigation. Cellular expression of antigens was examined by indirect immunoperoxidase (IP) assay using MAbs 4A9 and 1A10 against formalin-fixed, paraffin-embedded sections of normal and tumor tissue. Of 25 perianal gland carcinomas, 4A9 antigen was expressed in 100% and 1A10 antigen in 84%. In contrast, perianal gland adenomas were negative for both antigens, and little or no reactivity was detected with normal perianal glands. With eight perianal gland tumors, diagnosis of carcinoma versus adenoma was histologically equivocal, while IP assays consistently revealed focal expression of the 4A9 and 1A10 antigens in these tumors, and the staining coincided with foci of anaplastic cells having a high mitotic index. This group of tumors was designated adenoma/carcinoma in situ. Results suggest that 4A9 and 1A10 antigens are markers of carcinoma and malignant transformation in canine perianal gland tumors, and can be very useful as diagnostic reagents where the identification of carcinoma versus adenoma requires additional clarification beyond routine histopathological examination.