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Using T cells to target malignant brain tumors

Cellular immunotherapies that specifically target malignant tumors are thought to be a promising approach in cancer medicine. However, a basic requirement for this kind of targeted immunotherapy is to identify target molecules that are found exclusively on the tumor cells and are recognized by the immune system.

Malignant gliomas are incurable brain tumors that spread in the brain and cannot be completely removed by surgery. "Gliomas are very difficult to treat, and the lack of suitable target structures is a considerable challenge for developing immunotherapies," explained Lukas Bunse, an immunologist at the DKFZ and a doctor at the University Hospital Mannheim (UMM).

Using an experimental mouse model, Lucas Bunse and his team have now demonstrated for the first time that transgenic T cells targeting tumor neoepitopes can be used to treat gliomas.

Figure: Representative immunofluorescence images showing high T cell infiltration of cytotoxic CD8+ as well as helper CD4+ T cells in A2.DR1 glioma in the brain of adult A2.DR1 mice, making this model suitable for targeted immunotherapeutic interventions. CD8 = Staining against CD8+ lymphocyte cells; CD4 = staining against CD4+ lymphocyte cells; CD3 = staining against CD3+ which is involved in activating both CD8+ and CD4+ cells and serves as marker for T cells. Figure published in Kilian et al., Clinical Cancer Research 2021

Press release of the German Cancer Research Center in Heidelberg (English Language):
15.11.2021 Using T cells to target malignant brain tumors

Press release of the Medical Faculty Mannheim (German language):
15.11.2021 Mit T-Zellen gegen bösartige Tumoren

Original scientific publication:

T cell receptor therapy targeting mutant capicua transcriptional repressor in experimental gliomas.
Michael Kilian, Mirco Friedrich, Khwab Sanghvi, Edward Green, Stefan Pusch, Daisuke Kawauchi, Martin Löwer, Jana K Sonner, Christopher Krämer, Julia Zaman, Stefanie Jung, Michael O Breckwoldt, Gerald Willimksy, Stefan B Eichmüller, Andreas von Deimling, Wolfgang Wick, Felix Sahm, Michael Platten, Lukas Bunse
Clinical Cancer Research 2021,
DOI: http://clincancerres.aacrjournals.org/content/early/2021/11/01/1078-0432.CCR-21-1881