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Contenido archivado el 2024-05-14

Serological identification of human tumor antigens as a basis for specific active immunotherapy of human neoplasms

Objetivo

Objectives:
The development of specific vaccination approaches for immunotherapy of human neoplasms highly depends on the availability of human tumor antigens, which are exclusively expressed in human tumor cells. The aim of this proposal is to identify and characterize new tumor antigens using the SEREX (serological analysis of recombinantly expressed tumor antigens) approach.

SUMMARY: The development of specific vaccination approaches for immunotherapy of human neoplasms highly depends on the availability of human tumor antigens, which are exclusively expressed in human tumor cells. The aim of this proposal is to identify and characterize new tumor antigens using the SEREX (serological analysis of recombinantly expressed tumor antigens) approach. The first part of the study deals with the molecular identification of new tumor antigens in a defined spectrum of human neoplasms. We will focus on neoplasms which are difficult to analyse by T-lymphocyte based methods since the SEREX approach does not depend on the availability of specific T cell clones and cultured tumor cell lines. This will include breast carcinomas, prostate carcinomas, colon carcinomas and lung carcinomas. These neoplasms represent over 60% of the malignant diseases of the adult, but only a few antigens have been identified, which are expressed in these types of tumors.

The initial molecular characterization of new antigens will involve sequence analysis, expression analysis at the transcriptional level and genomic investigations including the localization and cloning of the genes coding for the identified transcripts. The precise analysis of expression and subcellular localization of the tumor antigens will be achieved by immunocytological and immunohistological analysis using monoclonal antibodies. In the second part of the project we will investigate CD4+ and CD8+ T-lymphocyte responses to the serologically identified antigens. The aim of this part is to define the antigenic peptides, which are derived from endogenous and exogenous processing of identified new tumor antigens. The defined peptides and recombinantly expressed antigens will be used for the in vitro stimulation and expansion of specific T lymphocytes. Established T cell clones will be tested for their ability to recognize and lyse antigen expressing tumor cell lines. Defined groups of healthy individuals and tumor patients will be screened for the presence of peptide specific T lymphocytes. The third part of the proposed project will involve a pilot immunization study of a small group of tumor patients using defined peptides or recombinantly expressed whole antigens. The results obtained by these investigations will form the basis for the consecutive application of identified antigens as cancer vaccines in controlled clinical studies.

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Coordinador

Universität des Saarlandes
Aportación de la UE
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Dirección

66421 Homburg / Saar
Alemania

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Participantes (4)

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