Vaccination with Apoptotic B Leukemia Cells Loaded Antigen Presenting Cells in Chronic Lymphoid Leukaemia
Coordinating Institution:
Centre Hospitalier de Luxembourg ,
CRP Sante
From: 01/03/2003
To: 28/02/2006
Budget: 243,257.00€
Contact(s):
Berchem Guy
Summary
Despite the still poorly understood complexity of tumour-host immune interactions, the use of cellular vaccines has made it possible to reliably generate tumour antigen specific T cells, both in animals and humans. Induction of productive T cell immunity requires efficient presentation of peptide antigens by professional antigen-presenting cells (APC). Although dendritic cells (DCs) have been selected as the “APC of choice” for immunotherapy, the complexity and cost of preparation of DC precursors and generation of functional DCs limits their utility as APC for the ex vivo generation of antigen specific T cells. In this project our laboratory developed a new vaccination strategy using B lymphocytes of peripheral blood from chronic lymphoid leukemic patients as APCs. These cells, re-injected in the donor after in vitro pulse with autologous apoptotic B cells, should induce a specific cytotoxic response against cancer cells. In 2005, the phagocytosis level of apoptotic B lymphocytes by APC was quantified using flow cytometry after membrane cell staining. These experiments were done on different patient cells in different culture conditions.
The results showed low levels of phagocytosis and highlight the need for a better characterisation of CLL cells. Therefore, extended phenotyping in CD markers was implemented in the cytoflow core facility and a collaboration with the Curie Institute was started to develop in Luxembourg a global analysis of the genome of tumour cells by a molecular approach using comparative genomic hybridization-array (CGH). CGH array identifies the regions of the genome that are amplified or deleted in tumours on DNA chips. In order to improve the use of this cellular therapy in clinical trial, obtention of APC with soluble CD40 ligand was tested.