Novel therapies for ALK tumours: ALK vaccination and immunotherapy

University of Torino

Dr. Roberto Chiarle

Supervisor

Publication Link

In vivo models of ALK-driven tumors and ALK-targeted immunotherapy

Research Interest

Roberto Chiarle has wide expertise in cellular biology, immunology, and molecular biology. He holds clinical qualifications for haematopathology and is currently the recipient of a double appointment as Full Professor and clinical physician at the University of Torino and as Associate Professor at Harvard Medical School. RC is a pioneer in the field of ALK-related lymphoma having generated one of the first mouse models of ALK-induced ALCL. His research aims at therapeutic targeting of ALK by means of specific inhibitors, drugs and immunotherapy. His objectives are therefore to improve our understanding of the molecular mechanisms of

  • ALK-driven transformation with in vitro and in vivo models
  • Mechanisms of chromosomal translocation formation in different tissues
  • Cancer Immunotherapy of ALK-driven cancers

Ines Mota

Research student

 

Research Interest

My name is Inês Mota. I hold a bachelor’s degree in Biomedical Science and a Master degree in Hematology and Immunology. I have been working in the Cancer Research Center of Salamanca (Salamanca, Spain) as research assistant since 2012.

In the ALKATRAS PhD program I will focus on the “Novel therapies for ALK tumors: ALK vaccination and immunotherapy” project in the Dr. Roberto Chiarle Laboratory in Turin (Turin, Italy). We are interested in ALK-specific cancer immunotherapy. A vaccination protocol that generates a strong ALK-specific immunization has been developed. Our major goal is establish the ALK vaccine as an additional powerful therapy to treat different ALK-positive tumors (Anaplastic Large Cell Lymphoma; Non-Small Cell Lung Cancers) and improve the response and remission rates of patients treated with ALK-inhibitors together with the ALK-vaccine.
Research description

We designed a DNA-based ALK vaccine directed against the cytoplasmic portion of ALK that is invariably translocated in ALK-rearranged tumours. The ALK vaccine has been highly efficient in inducing a specific tumour immune response that blocks the growth of ALK – rearranged lyphoma and NSCLC in precinlincal mouse models. In order to develop an ALK vaccine to be utilized as treatment for human patients we aim to optimize the ALK vaccine for human use. We will compare the efficacy of DNA-based and Synthetic Long Peptides (SLPs)- based ALK vaccines.

In principle, SLP will be preferable for use in humans. We will also determine the efficacy of combination protocols of ALK vaccine and ALK inhibitors in mouse models of NSCLC and neuroblastoma and assess the efficacy of ALK vaccines combined with additional immunotherapies such as anti-CTLA-4 or anti-PD-1/PD-L1 in mouse models of NSLCL, ALCL and neuroblastoma. Given the availability of immune checkpoint bloackade antibodies for human use, these results would help to determine the optimal combination with ALK vaccine, ALK inhibitors and immunotherapy for clinical use.

Expected Results:
Establish the ALK vaccine as an additional powerful therapy to treat different ALK-positive tumours; improve response and remission rates of patients treated with ALK inhibitors together with the ALK vaccine.

Planned secondment(s):
Year 1: Galkem (PO#4) – development and assessment of ALK inhibitors – 1 month;
Year 2: Justus-Liebig University, Giessen (B#11) – access to model systems investigating the ALK autoantibody response in patients (particularly, patient serum) – 1 month

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