Several tumor associated antigens have been shown to be able to induce an immune response. The identification of such antigens and the effector mechanisms involved is a first step for the development of useful cancer vaccines. PEM is a glycoprotein localized on the luminal surface ofmost simple epithelia. In cancer cells it is overexpressed and undergoes a process of aberrant glycosylation. Cryptic epitopes within the core protein of the extracellular domain are therefore exposed and could be a target for an immune response. An MHC unrestricted T cell response mediated by CD8 cells was described and explained by the particular structure of the molecule made up of tandem repeats (TR). Lymphocytes from tumor draining lymph nodes from patients with gynecological malignancies were utilized to study both the humoral and cellular immune responses of these patients. The human antibodies produced by these patients were directed against different epitopes within the TR sequence of PEM and were able to recognize the tumor associated glycoforms of the molecule. T cell clones were isolated that were able to proliferate in the presence of specific peptides corresponding to the TR of PEM presented by autologous B cells. The functional analysis of these clones revealed a Th phenotype. The possible contribution of T helper cells in generating and maintaining anti-tumor immunity opens new possibilities for effective immunological approaches in cancer therapy. Supported by AIRC and CNR “ACRO”. A.R. is supported by AIRC.

40 Immune response to the polymorphic epithelial mucin (PEM)

Nuti, M.;Petrarca, C.;
1995

Abstract

Several tumor associated antigens have been shown to be able to induce an immune response. The identification of such antigens and the effector mechanisms involved is a first step for the development of useful cancer vaccines. PEM is a glycoprotein localized on the luminal surface ofmost simple epithelia. In cancer cells it is overexpressed and undergoes a process of aberrant glycosylation. Cryptic epitopes within the core protein of the extracellular domain are therefore exposed and could be a target for an immune response. An MHC unrestricted T cell response mediated by CD8 cells was described and explained by the particular structure of the molecule made up of tandem repeats (TR). Lymphocytes from tumor draining lymph nodes from patients with gynecological malignancies were utilized to study both the humoral and cellular immune responses of these patients. The human antibodies produced by these patients were directed against different epitopes within the TR sequence of PEM and were able to recognize the tumor associated glycoforms of the molecule. T cell clones were isolated that were able to proliferate in the presence of specific peptides corresponding to the TR of PEM presented by autologous B cells. The functional analysis of these clones revealed a Th phenotype. The possible contribution of T helper cells in generating and maintaining anti-tumor immunity opens new possibilities for effective immunological approaches in cancer therapy. Supported by AIRC and CNR “ACRO”. A.R. is supported by AIRC.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11564/787731
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