Translational Soft Tissue Sarcoma Research

Research Topics

Cooperative Weichteilsarkom Studiengruppe (CWS) is one of the three world-wide soft tissue sarcoma study groups to optimize treatment of children, adolescents and young adults with rare soft tissue sarcomas and benign soft tissue tumors. CWS countries are Austria, Switzerland, Sweden, Finland, Poland and Germany. CWS collaborates with the European pediatric Soft Tissue Sarcoma Study Group EpSSG and Children`s Oncology Group COG as international partner in the United States.

The CWS study center and the organization of the Soft Tissue Sarcoma Registry (SoTiSaR and the upcoming SoTiSaR 2.0) is located at Klinikum Stuttgart, Olgahospital and the University Children's Hospital Tübingen, Chair is Prof. Dr. Monika Sparber-Sauer, Prof. Dr. Martin Ebinger is Co-Chair of the CWS group.

The clinical reference consultation for patients included in the European Soft Tissue Sarcoma Registry (SoTiSaR and the upcoming SoTiSaR 2.0) takes place for local treatment in the weekly tumor web-based conference. Molecular and translational research as well as new immunological approaches are most important to improve future classification of sarcoma and treatment of sarcoma patients. The centers Heidelberg, Tübingen and Frankfurt are affiliated research partners at highest level.

Together with the Peter Lang group we are conducting PerVision, a prospective multicenter phase I/II study to evaluate clinical safety, immunological response to a patient-individualized peptide vaccine in pediatric and young adult metastasized fusion-driven sarcoma patients including the fusion-spanning protein. The trial is financed by the DKTK (German Cancer Consortium).

Inclusion criteria:

Stage 1: Metastatic fusion-driven rhabdomyo-, Ewing- and synovial sarcoma patients (age > 2 and < 40 y) in first or second complete remission (CR) or partial response (PR). WES and RNAseq data of the gene fusion must be available (registration to INFORM, MASTER or HEROES-AYA encouraged).

Stage 2: CR or stable PR including status post local therapy of remaining residua (PRplus) at end of standard treatment (including maintenance therapy).

Vaccine generation: Tumor-specific mutations and gene-fusions will be identified by WES and RNASeq. Neoantigens will be predicted based on individual HLA binding probabilities determined in silico. The neopeptide with the highest binding prediction score will be selected. A second peptide will be derived from the sarcoma-specific fusion breakpoint. The individualized peptide cocktail will be administered s.c. (adjuvant XS15; IPX vaccine).

Study intervention: The standard treatment is not part of the trial. One month after end of standard treatment patients will receive the IPX vaccine: Three vaccinations at week 0, 4, 8, followed by 16 weeks of follow-up. Duration of the interventional Stage 2 for individual patients is 6 months with 7 visits. Total trial duration is 4 years. It is estimated that 30 patients will be screened, and 21 patients included.

Aims: Primary aim of this study is to evaluate immunogenicity (specific T cell response at week 12) along with safety/toxicity of the IPX vaccine.

Secondary aims: To compare the immunogenicity of the predicted neopeptide with the peptide derived from the sarcoma-specific fusion breakpoint; to compare T-cell responses at week 24 with those at week 12; to evaluate EFS and OS at week 24; to evaluate quality of life during the trial; to correlate inducibility of immune responses with clinical patient characteristics.

In cooperation with the Peter Lang group and the Christian Seitz group we are evaluating the possibilities of a tailored immunotherapy against advanced soft tissue sarcoma including anti-B7-H3 (CD 276) antibody constructs connected with interleukins or adapter-CAR-T-cell system.