RG Gary/Aigner

Medicine 5

Head of Department:
Prof. Dr. med. Andreas Mackensen

RG Cellular Immunotherapy

Team RG Gary/Aigner and AG RG Völkl


Staff: Dr. Michael Aigner, Carolin Strobl, Stefanie Schaffer, Dr. Regina Gary, Stephanie Moi, Prof. Dr. Andreas Mackensen

The research group of Dr. Regina Gary and Dr. Michael Aigner is engaged in the exploration and understanding of new cellular therapies; Research focus is the enhancement and development of T-cell immunotherapy.

Adoptive T-Cell Transfer

Adoptive T-cell therapy aims the elimination of malignant cells by transferring immune cells. An impressive confirmation of the efficacy of transferred lymphocytes is provided in allogeneic stem cell transplantation (SCT) in form of either bone marrow transplantation or the transfer of collected stem cells by leukapheresis after G-CSF mobilization of the allogeneic donor. In acute and especially chronic myeloid leukemia (CML) the graft-versus-leukemia effect - which is predominantly mediated by T-lymphocytes - is the central principle of the therapeutic SCT.

The first clinical trials of adoptive lymphocyte transfer indeed show a therapeutic effect on the tumor growth. However, the therapeutic efficacy is limited so far, so that an improvement of existing or the development of completely new approaches is needed.

In addition, T lymphocytes are critically involved in the control of viral diseases. Particularly in the first period after SCT patients often do not show sufficient immune protection which leads to the development of many serious and difficult-to-treat infections with viruses as Cytomegalovirus (CMV) or Epstein-Barr viruses (EBV).

 Our aim is the selection and expansion of beneficial T lymphocytes under Good Manufacturing Practice (GMP) conditions, which allows us the application of these cellular products in clinical trials. Additionally, we are working on new strategies to improve the antigen-specificity and the function of the in vitro expanded T lymphocytes.

 We were able to develop a protocol that allows us to collect, expand and analyze CMV/EBV-reactive T cells for the prevention and treatment of viral disease after SCT in the context of a clinical trial (Phase I/IIa).

Tumor metabolism

Tumors develop various mechanisms to escape the control of the immune system. They inactivate either specific immune effector cells or potentially anti-tumoral effector mechanisms. There are various known "Immune Escape" mechanisms that are directed against a T-cell mediated immune response. The exploration of tumor metabolism and its effect on the adaptive immune system has moved in the center of interest in tumor immunology. It is known, for example, that in the hypoxic environment of a tumor high levels of lactic acid are produced through aerobic glycolysis, which leads to decreased T-cell activity, resulting in a significantly reduced cytotoxic function.

We are currently working on the analysis of other tumor metabolites and the mechanisms of their inhibitory activities against immune cells and to use this knowledge to develop improved T-cell therapies.

Our long term goal is the improvement of adoptive T-cell therapy and that our results will form the basis for a new clinical trial of adoptive T-lymphocyte therapy in patients with malignant diseases.

Funding by DFG (SFB 643, KFO 262), BayImmmuNet and ELAN.

 
Contact
Dr. rer. nat. Regina Gary
DECT: +49 9131 85-43162
e-mail: regina.gary@uk-erlangen.de
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Dr. Michael Aigner
DECT: +49 9131 85-43160
e-mail: michael.aigner@uk-erlangen.de
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Summary