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Focus of Research
Our group is actively developing immunotherapeutics, building on a proven track record of transferring basic experimental science into the clinic. We are pursuing the following projects:
1. Dendritic cells to activate the immune system of patients with cancer
Dendritic cells are the most potent “professional” antigen presenting cells, and are therefore of interest in the activation of the immune system to attack cancer cells. A vaccine using gene-modified dendritic cells was developed by our group, and a clinical phase I/II trial with pancreatic or breast cancer patients was performed under the guidance of G. Pecher (1). Currently, the group works on the optimization of this strategy.
2. Development of chimeric antigen receptor (CAR) modified immune cells for the immunotherapy of cancer
A rapidly emerging approach to fight cancer is the use of chimeric antigen receptor (CAR) modified immune cells. In this approach, T-cells from cancer patients are genetically engineered to produce tumor antigen-specific receptors on their surface, thereby enabling immune cells to attack cancer cells when reinfused into the patients. One main focus of our research group is the development of such CAR modified cells for the therapy of patients with hematological and oncological diseases (2-4). A CAR receptor recognizing the Carcinoembryonic Antigen (CEA) on tumor cells developed by our group has been brought from bench to bedside under the guidance of G. Pecher. A clinical phase I study using this receptor for CAR T-cell therapy in patients with colorectal cancer showed the feasibility of this approach (5). In patients with solid tumors, CAR T-cell therapy must overcome several obstacles, including tumor stroma related immunosuppression, tumor escape mechanisms, and limited persistence of immune cells at the tumor site. Our group is developing next generation CARs in order to overcome these obstacles.
3. Investigating the role of Beta-(1-3),(1-6)-glucan in cancer therapy
Beta-glucans are polysaccharides which appear, for instance, in the cell wall of yeast. They activate the Dectin-1 pattern recognition receptor and they can induce the expression of a unique pattern of molecules on dendritic cells. Our research group is investigating the use of Beta-(1-3),(1-6)-glucan in the therapy of malignant diseases (6-8).
4. Investigating the role of the tumor microenvironment
Another focus of our group is investigating the interaction among the cells of the tumor microenvironment in order to overcome stroma-related immunosuppression. Three dimensional culture systems of stroma cells are being used to test drugs and immunotherapeutics.
1.Pecher G., A. Häring, L. Kaiser and E. Thiel. 2002. Mucin gene (MUC1) transfected dendritic cells as vaccine: results of a phase I / II clinical trial. Cancer Immunol. Immunother. 51: 669-673
2.Schirrmann T. and G. Pecher (2001). Tumor-specific targeting of a cell line with natural killer cell activity by asialoglycoprotein receptor gene transfer. Cancer Immunol Immunother. 50: 549-556
3.Schirrmann T. and G. Pecher (2002) Human natural killer cell line modified with a chimeric immunoglobulin T-cell receptor gene leads to tumor growth inhibition in vivo. Cancer Gene Ther. 9: 390-398
4.Schirrmann T. and G. Pecher (2005). Specific targeting of CD33+ leukemia cells by a natural killer cell line modified with a chimeric receptor. Leukemia Res. 29: 301-306
5.Zhang C., Wang Z., Yang Z., Wang M., Li S., Li Y., Zhang R., Xiong Z, Wein Z., Shen J., Luo Y., Zhang Q., Liu L., Qin H., Liu W., Wu F., Chen W., Pan F., Zhang X., Bie P., Liang H.J., Pecher G.* and C. Qian*. 2017. Phase I escalating-dose trial of CAR-T therapy targeting CEA+ metastatic colorectal cancers. Mol Ther. 25: 1248-1258 *joined senior authorship
6.Harnack U., Eckert K., Fichtner I. and G. Pecher. 2009. Oral administration of a soluble 1-3, 1-6 beta-glucan during prophylactic survivin peptide vaccination diminishes growth of a B cell lymphoma in mice. Int Immunopharmacol. 9: 1298-1303
7.Harnack U., Eckert K. and G. Pecher. 2011. Beta-(1-3),(1-6)-D-glucan Enhances the Effect of Low-Dose Cyclophosphamide Treatment on A20 Lymphoma in Mice. Anticancer Res. 31: 1169-1172
8.Harnack U., Eckert K. and G. Pecher. 2011. Role of Soluble β-(1-3), (1-6)-D-glucan from Saccharomyces cerevisiae in the Murine P388 Ascites Tumor Model. In Vivo. 25: 185-190
Für mehr Details nutzen Sie bitte auch die Forschungsdatenbank der Charité.