Summary

The Laboratory for Translational Cancer Immunology develops immunotherapies for malignant neoplasia, with a special focus on acute leukemia and B-cell lymphoma. We seek to better understand mechanisms of action and resistance with the goal to identify predictive biomarkers for selecting the suitable immunotherapy for each individual patient.

Major research topics:

Identification & Characterization of Target Antigens

A great challenge remains to identify surface antigens that are specific for the tumor and are only expressed at very low levels on healthy tissue. We are continuously exploring novel target antigens for antibody-based and CAR T cell approaches. Utilizing flow cytometry, proteomics and mass spectrometry we validate known target antigens and explore novel target structures.

Antibody-based Immunotherapy & CAR-T cells

T-cell engaging antibodies are a novel format of antibodies that bind to a surface antigen preferentially expressed on the malignant cell and with the other arm recruit T cells through the CD3 receptor. The format has already proven clinical efficacy with approval of a CD19-targeting antibody construct in acute lymphoblastic leukemia. Currently, various T-cell recruiting antibody constructs are being developed for different tumor entities. We seek to understand the mode of action and innate and adaptive resistance mechanisms. Our findings have already been translated in early Phase I clinical trials conducted at the University Hospital of the LMU Munich (Med. Klinik III).

Chimeric Antigen receptor (CAR) T cells include genetically engineered antigen receptors that combine the single chain variable fragment (scFV) of an antibody directed against a tumor associated antigen with intracellular signaling domains of T cells. Identification and generation of suitable scFV and functional characterization of appropriate constructs for treatment of myeloid malignancies is being explored.

Therapeutic Vaccination & Checkpoint Blockade

Using a TLR7/8 agonist, we have developed a GMP-compliant 3-day protocol to differentiate monocytes of intensively pretreated AML patients into highly functional, therapeutic dendritic cells (DCs). A phase I/II proof-of-concept study was initiated using TLR7/8-matured DCs as post remission therapy of AML patients with a non-favorable risk profile in CR or CRi after intensive induction therapy (NCT01734304).

We aim to improve vaccine efficacy by combinatorial approaches using hypomethylating agents and monoclonal antibodies against checkpoint molecules with the idea to unleash pre-existing anti-tumor T cell responses.

Immune Monitoring & Prognostic/Predictive Biomarkers

Our strategy is to develop immunotherapeutic concepts into early phase I trials and accompany running clinical trials to understand mode of action and mode of resistance. Our particular focus is on close immune monitoring of T cell subsets, NK cells and soluble factors during the course of treatment. Using phenotypic and genotypic characterization of the immune contexture in conjunction with quantification of residual disease is the basis for identifying prognostic and predictive biomarkers.