Clemens-Martin Wendtner, M.D. University of Cologne (Germany)

Evaluation of antigen-specific immune responses in the context of gene-modified tumor cell vaccines for CLL

Grant Awarded in 2008

Abstract:

There is evidence from cell culture experiments that CLL is in part caused by an impaired immune system of the individual patient, i.e. non-functional T-lymphocytes that are not able to attack the tumor cell. In recent years, different strategies were established to overcome this so called T-cell anergy, or lack of energy.

One promising approach with initial evidence of clinical efficacy is the use of gene-modified CLL cells, i.e. transferring co-stimulatory molecules in the CLL cells by gene vectors to make the tumor cell recognizable as a target for T-lymphocytes. Within the CLL Alliance, we will participate in gene therapy trials using different vector systems (adenovirus, adeno-associated virus) to genetically modify the CLL cell.

Our specific aim is to assess the immune reaction of the patients towards these vaccines. In the context of clinical trials, we will look for immune responses against molecules and peptides presented at the surface of the CLL cells. This analysis will be based on previous work where we identified several of these immunogenic structures on the CLL cells in lab experiments (fibromodulin, CD229, MDM2 etc.).

We will also check the profile of genes expressed in immune cells, i.e. in T-lymphocytes, before and after vaccination and correlate this with the clinical outcome of the patients. This will give us insight as to which important genes are necessary for an effective immune therapy.

In the future, we might be able to predict treatment outcomes for the individual patient. Once we are able to define what the critical targets are on the CLL cells and we know the immunologic profile of patients who benefit from this kind of gene therapy intervention, we might be able to further design more tailored vaccination therapies for patients with CLL.