The Thurner group focuses on the role of misguided immune responses in cancer, inflammation, and infections. We bring clinical questions into our laboratory for which we have expertise.
Simplified scheme of the adaptive immune response.
We are searching for external triggers of B-cell lymphoma. These can be autoantigens that are very unusually postranslationally altered, such as the hyper-N-glycosylated SAM-domain of SAMD14
and neurabin I – two CNS proteins – as targets of B-cell receptors of primary CNS lymphoma. These unusual changes in proteins (atypical post-translationally modified isoforms) can lead to a
peripheral breach of tolerance and provoke a chronic immune response, in the context of which malignant transformation of B-cells can occur. Examples include primary CNS lymphoma, DLBCL
(hypophosphorylated Ars2 as antigen), or LRPAP1 in mantle cell lymphoma. Of interest, lymphoma cell lines keep the BCR-reactivity against these antigens despite decades in culture. Beside altered
self-proteins, antigens of infectious origin can also be involved, such as the dual stimulatoon by Moraxella catarrhalis RpoC via the Fab-fragment and MID/hag via the Fc-fragment of IgD+
Lymphocyte predominant cells in Hodgkin lymphoma (nodular lymphocyte predominant subtype). Interestingly this occurs in the context of a permissive HLA-DRB1-04 haplotype, and these LP-cells have
ultralong CDR3. For these projects we have been cooperating very good with the hematopathology group of Sylvia Hartmann and Martin-Leo Hansmann and with the department of microbiology of Sören
Becker and the department of virology of Sigrun Smola.
We are looking for reasons of poor responses to immunotherapies in cancer. Here, the focus is on effector cells (NK cells, cytotoxic T cells). We analyze these mechanisms in CD20 or CD38
mediated ADCC, bispecific antibodies (CD20/CD3 or CD19/CD3), with CAR-T cells, and in allogeneic SCT. We work closely with the group of Markus Hoth from Biophysics department, as well as with the
group of Frank Neumann from the Carreras Center. For clinical correlations, we collaborate with Marita Ziepert and Bettina Altman from IMISE Leipzig.
We are searching for new, specific target antigens for immunotherapies for difficult to-treat tumor types. In addition to hematological neoplasms, we also investigate solid tumors. After
identifying these antigens, we develop for specific antibody constructs and integrate them into immunotoxins or bi-specific antibodies. We produce bi-specific antibodies using the IgG4-based
controlled Fab-Exchange method. We closely cooperate with the group of Moritz Bewarder in the Carreras Center and the AG Hoth of Biophysics in Homburg.
With our translational work, we also try to provide the basis for early clinical trials, especially for rare or neglected diseases in our view, such as Burkit lymphoma or primary
CD20-negative aggressive B-cell lymphomas (often associated with HIV or immunosuppression). We closely cooperate with the group of Frank Neumann of the Carreras Center and with the group of
Sigrun Smola of the department of virology.
We are interested in misguided immune responses that can result in excessive inflammatory reactions and the underlying mechanisms. This is of interest in the field of cell-therapy mediated
hyperinflammation (CRS, ICANS), as a rare phenomenon in hematology and oncology, or as a side effect of checkpoint-inhibitor therapy. We have described a class of autoantibodies that bind and
neutralize anti-inflammatory mediators in the blood, thus shifting the inflammation balance towards inflammation. The cause of these antibodies is often unusual changes in the respective
anti-inflammatory mediators (atypical post-translationally modified isoforms - note similarity to driver autoantigens in B-cell neoplasms), leading to immunogenicity. We work very closely with
the team of Christoph Kessel, as well as with rheumatologists, cardiologists, pulmonologists, gastroenterologists, infectious disease specialists, pediatricians, and even psychiatrists.
We are also interested in B-cell-mediated diseases or autoimmune diseases like TTP, inhibitor hemophilia, aplastic anemias, vasculitides, and other pathogenically related diseases, including
non-hematological/oncological areas. If you have a good idea for a collaboration, please feel free to contact us.
Prof. Dr. Lorenz Thurner
Onur Cetin, (mantle cell lymphoma LRPAP1, research on ineffectve lytic granules in the context of rituximab-mediated ADCC in the RICOVER-60 study)
Achilles Ntarallas, (HIV-associated lymphomas)
Vadim Lesan, (lymphoma, cell therapy)
Dr. Igor Kos (PCNSL and AITL and infections, inhibitor hemophilia, autoimmunity, GVHD)
Dr. rer nat. Klaus-Dieter Preuss (specialist for PTM, chemist, problem solver)