Analysis of the presentation of tumour associated antigens by tumour and antigen presenting cells with newly developed recombinant single chain antibodies with T cell receptor-like specificity

• Applicant: Professor Peter Walden, Ph.D.
• Subject Area: Dermatology
• Term: from 2001 to 2004
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5358847

Cytotoxic T cells play a major role in anti-tumour immunity. They recognise peptides derived from cellular proteins as complexes with MHC class I molecules and can detect structural as well as regulatory alterations in tumour cells. Although a number of tumour associated T cell epitopes have been identified, nothing is known about the number of specific MHC peptide complexes on the tumour cells or the spectrum and distribution of antigen presenting cells in the tumour micro-environment and draining lymph-nodes. The projected research aims to develop and utilise recombinant single chain antibodies (scFv) with T cell receptor (TCR) like specificity for tumour-associated MHC peptide complexes. Uniformly peptide loaded recombinant MHC class I molecules shall be used as antigens to select such scFvs from highly complex phage display libraries. They will then be randomised and re-selected to obtain high affinity reagents, analysed for their specificities and capacity as TCR-like recognition moieties. They shall be used to stain tumour cells isolated from patients as well as histological sections of tumours and draining lymph-nodes to quantify the specific MHC peptide complexes per cell, to characterise the specific antigen presenting cells and analyse their distribution. This research will contribute significant information to the understanding of antigen processing by tumour and antigen presenting cells, and of the interrelationship of tumour and immune system.

• DFG Programme: Research Grants
• International Connection: Israel
• Participating Person: Professor Yoram Reiter, Ph.D.