Özlem Türeci

Serological identification of human tumor antigens

Using the antibody repertoire of cancer patients for the systematic search for human tumor antigens, a plenitude of new human tumor antigens has been identified demonstrating that many human tumors elicit multiple immune responses in the autologous host. The abundance of serologically defined human tumor antigens facilitates the identification of T cell dependent antigens and provides a basis for peptide and gene therapy vaccine strategies in a wide variety of human cancers.

Recognition of human tumors: SEREX expression cloning to identify tumour antigens

The search for tumor antigens which are able to elicit specific immune responses in the tumor-bearing host is one of the cardinal quests in tumor immunology. The knowledge of their molecular nature provides us not only with potential targets for immunotherapeutic interventions against neoplastic cells, but also provides us with new disease markers and new insights into the molecular mechanisms of malignant transformation.

Identification of Human Tumor Antigens Using the B-Cell Repertoire

Specific vaccines for the immunotherapy of human neoplasms require specific human tumor antigens. While efforts to identify such antigens by the analysis of the T-cell repertoire yielded only few antigens, the application of SEREX, the serological identification of antigens by recombinant expression cloning, has brought a multitude of new antigens. Several specific antigens have been identified in each tumor tested, suggesting that many, if not all human tumors elicit multiple immune responses in the autologous host. The frequency of human tumor antigens, which can be readily defined at the molecular level, facilitates the identification of T-cell dependent antigens and provides a basis for peptide and genetherapeutic vaccine strategies.

Discovery of Target Molecules for Cancer Immunotherapy by Genetic and Bioinformatic Approaches

It has been a long-standing vision of scientists studying tumor immunology to use the immune system’s effectors for the therapy of cancer by directing them against target molecules expressed selectively on tumor cells. Different genetic approaches for discovery of such target candidates have been developed over the last 15 yr and are being pursued. The classical approaches apply expression cloning using either cancer-reactive T-lymphocytes or autoantibodies in crude patient sera as probes to identify target molecules of spontaneous immune responses. Recent concepts utilizing high-density microarray analysis, subtractive library approaches, or in silico cloning aim at the identification of genes with cancer cell-associated expression and subsequently address the immunogenicity of such molecules with reverse immunology. This chapter summarizes the peculiarities of these approaches, reflects on rationale criteria for selection of vaccine candidates, and discusses how integrated discovery and validation strategies may assist in the delivery of suitable targets.