Defining the autologous immune response against ALK in children and adolescents with ALK-positive ALCL


Justus-Liebig University Giessen

Prof. Wilhelm Woessmann,
Dr. Christine Damm-Welk

Supervisor

Publication Link (WW)

Molecular diagnosis of childhood ALCL; Immune response to ALK in ALCL


Personal statement

Wilhelm Woessmann is a paediatric oncologist, co-chair of the NHL-BFM study group and an active member of the European paediatric NHL study group (EICNHL). His translational research includes biological risk factors, molecular biology and immune response against ALK in children with ALCL.

Serena Stadler

Research student

 

Research Interest

Serena is a PhD candidate for the ESR11 project in Gießen, Germany,under the supervision of Prof. Wilhelm Woessmann and Dr. Christine Damm-Welk. She will investigate the autologous immune response against ALK in children and adolescents with ALK+ALCL. She was born in Vienna, Austria, where she received a Bachelor´s degree in Genetics and Microbiology at the University of Vienna. Shecontinuedher studies in the Master´s program Molecular Biology with the focus on Molecular Medicine at the University of Vienna and received her Master´s degree in June 2016.Serenawas working at the Institute of Clinical Pathology at the Medical University of Vienna on interactions between colorectal cancer cells and cancer-associated fibroblasts during early stages of metastasis. She established a new in vitro3D co-culture model and could identify signaling pathways underlying colorectal cancer invasion into adjacent stroma.

Research description

 ALK+ ALCL patients can mount ALK-specific antibody- and T-cell responses against ALK. ALK-specific antibody titres inversely correlate with outcome suggesting a role of the immune response in tumour control. Within this clinical scientific framework we will characterize the CD8+ and CD4+ T-cell responses against ALK in patients as a prerequisite for the development of a vaccination strategy in an ethically approved study.

We aim to: Define the autologous CD4+ specific T-cell response in patients with ALK-positive ALCL; assess both antigen reactivity and HLA II restriction against NPM-ALK; characterize the NPM-ALK antigenic peptides resulting from antigen processing and presentation, to define the most suitable epitopes for vaccination strategies.

Expected Results:
Autologous CD4+ T-cell response will be expected in about 50% of analysed patients; HLA restriction will be defined in 50% of patients with an autologous response. NPM-ALK antigenic peptides will be defined for a minimum of 2 patients (e.g. 1 HLA-DR, 1 HLA-DQ).

Planned secondment(s):
Year 2: Cambridge Life Sciences (PO#9) – validation of patient serum for ALK antibodies – 1 month; Year 2: University of Turin (B#9) – Development of ALK vaccination protocols – 2 months

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