Target Discovery and Validation

Target discovery is the process of selecting suitable target molecules for the treatment of cancer and other diseases. Diverse influences may drive such structures to be activated or mutated, or bring about a gene fusion encoding a new target. Such targets may accumulate in certain tumor types, or in individual patients. Molecular datasets from NGS are an integral resource for target discovery.

TRON’s Expression & Cell Biology team scans enormous sequencing datasets generated from various tumors and healthy tissues to identify and assign highly specific targets to distinct tumor entities.  Our PCR Analytics, Medical Biochemistry and Biosampling experts confirm these targets by independent methods – qPCR and protein expression analysis. Furthermore, tumor cell lines are investigated for target expression. Suitable cell culture models are generated to evaluate functional relevance in vitro. In close collaboration with the IDC we select candidates to further assess their functional role in vivo and to explore potential antitumoral immune responses on exposure via vaccination or antibody treatment.

All results including a comprehensive literature survey are compiled into target and biomarker profiles, building a powerful toolbox for the development of new immunotherapy approaches.

Our targets have been included into several publications and various clinical trials:

Publications

Reinhard K, Rengstl B, Oehm P, Michel K, Billmeier A, Hayduk N, Klein O, Kuna K, Ouchan Y, Wöll S, Christ E, Weber D, Suchan M, Bukur T, Birtel M, Jahndel V, Mroz K, Hobohm K, Kranz L, Diken M, Kühlcke K, Türeci Ö, Sahin U. (2020) An RNA vaccine drives expansion and efficacy of claudin-CAR-T cells against solid tumorsScience. 367:446-453

Barea Roldán D, Grimmler M, Hartmann C, Hubich-Rau S, Beiβert T, Paret C, Cagna G, Rohde C, Wöll S, Koslowski M, Türeci O, Sahin U. (2020) PLAC1 is essential for FGF7/FGFRIIIb-induced Akt-mediated cancer cell proliferation. Oncotarget. 11:1862-1875.

Paret C, Simon P, Vormbrock K, Bender C, Kölsch A, Breitkreuz A, Yildiz Ö, Omokoko T, Hubich-Rau S, Hartmann C, Häcker S, Wagner M, Roldan DB, Selmi A, Türeci Ö, Sahin U. (2015) CXorf61 is a target for T cell based immunotherapy of triple-negative breast cancer. Oncotarget . 6:25356-25367.

 

Clinical Studies

NCT02410733 (2015-2022)

Evaluation of the Safety and Tolerability of i.v. Administration of a Cancer Vaccine in Patients With Advanced Melanoma (Lipo-MERIT)

NCT02316457 (2016 – 2020)

RNA-Immunotherapy of IVAC_W_bre1_uID and IVAC_M_uID (Triple Negative Breast Cancer)

NCT04382898 (2019-2023)

PRO-MERIT (Prostate Cancer Messenger RNA Immunotherapy) (PRO-MERIT)

 

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