List of participants
Cancerna International Cooperation
The CANCERNA team leaders chart (Figure 10) shows the world-renowned scientists that are contributing to this project. This extraordinary and gender balanced group of scientists is what provides CANCERNA the potential to achieve ground-breaking outcomes. Together, the CANCERNA partners hail from six different countries, including Belgium(1) Germany (2), Israel (5), Netherlands (1), Portugal (1), and Spain (2), embodying international EU led cooperation. The diversity of the consortium is demonstrated in the type of organizations contributing to the project (Figure 11), including research organizations (4), SMEs (2), public bodies (3), large enterprise (1), and Secondary or higher education establishment (2). By synergizing their research and focusing their effort towards project goals, the CANCERNA partners are impacting the future of cancer treatment.
Cancerna International Cooperation
EC projects background
CANCERNA partners have vast experience leading and participating in EC funded projects. Overall, the participants in CANCERNA have taken part in over 1500 projects accepted for funding. This experience will allow the partners to manage and execute the project efficiently and effectively.
MACHINERY AND EQUIPMENT
SAMPLES & MODELS
Healthy donors and oncology patients-derived blood and tissue samples; Large bank of frozen tissues; Immune competent and immune deficient mouse models; PDX modelling; Phage display and hybridoma generation; Immune phage library generation
Project interdisciplinary and expertise
A strong feature of CANCERNA is the teaming-up of leading basic scientists (IMM, CGR, HUJI) and complex bioinformatics research (BIU, UKER) together with centres of a proven record in translational research (UKER, UAntwerp, IJC, VUMC) and clinical oncologists with strong background in basic and clinical cancer immunotherapy (HCRI, VUMC). Complementary to this team, CANCERNA has a translational branch of partners, that are able to translate the project results into off-the-shelf drugs and medical interventions (Merck, Immunyx, Gsap).
As a corollary, we have chosen two central cancers, that each represent a pressing medical need and a common denominator, being the centricity of defects in RNA processing as drivers of the malignant behaviour and the absence of a good immunotherapeutic option. Uveal melanoma represents a good model disease for the exploitation of the immunogenic power of abnormal RNAs. Unlike cutaneous melanoma, this melanocytic malignancy does not respond to ICI, it displays only a small amount of point mutations and preferentially metastasizes to the liver, a site which is viewed as an immune suppressive environment. This clinical reality drove us to select this tumour, which is top among cancers with SF mutations and therefore, provides us with a model for manipulating splicing products.
The second cancer is a hematologic malignancy, AML (and MDS), acute myeloid leukaemia (AML) is an aggressive hematologic cancer in which malignant myeloid precursor cells impair haematopoiesis and induce bone marrow failure. AML is the second most common type of leukaemia diagnosed in adults and, despite clinical efforts, the overall 5-year survival rate is around 25% and there is an unmet need for medical solutions. In addition to recurrent somatic mutations, truncations, and small translocations, the notion is that spliceosomal mutations in SRSF2, U2AF1 and SH3B1, in 10% of patients, phenocopy recurrent mutations despite wild-type sequences of the corresponding genes. We suggest to take advantage of this transcriptional vulnerability and to provoke the emergence of immunogenic sequencies that will increase the relevance of immunotherapeutic options in this disease.
A diverse and gender balanced consortium built towards project objectives
Figure 10 Cancerna Leading Team
Project advisory board and support
Adrian Krainer, PhD. St. Giles Foundation Professor; Cancer Center Deputy Director of Research; Cold Spring Harbor Laboratory. Wolf prize laureate Prof. Krainer’s expertise stems from over three decades studying RNA splicing mechanisms and regulation, the dysregulation of this process in the context of cancer and genetic diseases, and preclinical development of antisense therapeutics, including the FDA/EMA-approved drug Spinraza for spinal muscular atrophy.
Lynne E. Maquat, J. Lowell Orbison Endowed Chair, Professor of Biochemistry & Biophysics; Founding Director of the Center for RNA Biology, and Founding Chair of Graduate Women in Science at the University of Rochester, NY. Wolf prize laureate Dr. Maquat’s research focuses on the molecular basis of human diseases, with particular interest in mechanisms of mRNA decay.
Nir Hacohen, PhD. Director of the Center for Cancer Immunology at MGH; Founding member Board Institute RNAi Consortium; Co-director of the Broad Cell Circuits Program and NHGRI Center for Cell Circuits. Dr. Hacohen is an immunologist, geneticist and systems biologist focused on dגissecting the basic mechanisms of immunity, developing and applying genetic technologies that accelerate the study of the immune system, and deciphering and treating human diseases — including cancer and immune disorders – based on genomic approaches.
Omar Abdel-Wahab, MD. Member in the Human Oncology and Pathogenesis Program; Attending Physician on the Leukemia Service in the Department of Medicine at Memorial Sloan Kettering Cancer Center; and the Director of Memorial Sloan Kettering’s Center for Hematologic Malignancies. Dr. Abdel-Wahab’s research focuses on the role of genomic alterations and RNA processing in the pathogenesis of hematopoietic malignancies and other cancers.
Ron Weiss, PhD., Professor of Biological Engineering, Massachusetts Institute of Technology
Prof. Weiss is one of the pioneers of synthetic biology. He has been engaged in synthetic biology research since 1996 when he was a graduate student at MIT and where he helped set up a wet-lab in the Electrical Engineering and Computer Science Department. After completion of his PhD, Weiss joined the faculty at Princeton University, and recently returned to MIT to take on a tenured faculty position in the Department of Biological Engineering and the Department of Electrical Engineering and Computer Science.
Steven A. Rosenberg, MD., PHD., Chief, Surgery Branch, National Cancer Institute, NIH Dr. Rosenberg pioneered the development of effective immunotherapies and gene therapies for patients with advanced cancers. He has expressed support for CANCERNA and interest in project outcomes.
Project partners unique contribution to CDE
M. Carmo-Fonseca published 25 peer-reviewed papers in the past 5 years, including a commissioned review on “Targeting mRNA processing as an anticancer strategy” for Nature Reviews Drug Discovery. She is editor for The Journal of Cell Science and the RNA journal, and was elected President of the RNA Society for 2021-2022. She is regularly invited to give talks (including key note lectures) at international meetings, and to participate in dissemination events targeted to the medical community and pharmaceutical industry (in Portugal and Europe). Examples of public sessions organized at iMM that bring together scientists, medical doctors and patients: https://www.youtube.com/watch?v=5jLDXz9qHwI. Example of interview in Portuguese TV: http://bit.ly/AdmiravelMundoNovo1 and http://bit.ly/AdmiravelMundoNovo2
T. de Gruijl and H.J. Van der Vliet have a wide combined network of (pre-)clinical IO researchers and pharma/investors that will facilitate easy and rapid communication and dissemination (and eventual exploitation) of findings. Data will be published in high-impact IO journals and presented in major conferences; eventual valorisation will be implemented according to stipulations set out in the consortium agreement and together with the Tech Transfer Office of Amsterdam UMC (IXA).
The Melanoma and Cancer Immunotherapy Center at the Hadassah Hospital, and prof. Lotem’s lab as the leader of the center is at the forefront of innovative research and patient treatment. The Center has a significant impact on the management of cancer patients through the development of novel approaches to improve current immunotherapies. T Cell Therapy is one such immunotherapy that represents a highly promising and robust approach for the treatment of many cancers. As the coordinator of CANCERNA, HCRI contributes its expertise in TCR-T, vaccination, immune checkpoints, and splicing modification.
The Integrated Personalized and Precision Oncology Network (IPPON) that runs under Antwerp University develops novel personalized cancer therapies. Its main expertise in this project is working on immune checkpoints, RNA-engineered cell therapy and cancer vaccines.
The Department of Dermatology at UKER has outstanding experience in performing academia-initiated clinical trials in cellular cancer immunotherapy. The department established a non-genetic cell transfection platform to transfer chimeric receptors to T-cells and they hold the expertise to select suitable target antigens from genetic data. In this project, they contribute computer and RNA-based engineering of CART-T cells for therapy resistant uveal melanoma.
IJC is a reference centre for personalized medicine that applies new outstanding technologies such as Epigenomic and Proteomics to understand the pathogenesis and improve early detection and diagnosis, as well as to develop novel targeted therapeutics and innovative treatments for leukaemia and other blood malignancies. In this project, IJC contributes expertise in stem cell biology, developmental leukaemia and immunotherapy research.
HUJI is Israel’s premier university and leading research institution, ranked amongst the top 100 universities in the world. Prof. Karni’s research group focuses on RNA processing regulation and RNA therapeutics. More specifically, they research alternative splicing regulation in heath and disease, RNA processing misregulation in cancer initiation and progression and modulating RNA processing and alternative splicing for cancer therapy. As an expert for RNA-based cancer therapies, Prof. Karni is the scientific coordinator of CANCERNA.
CRG is an international biomedical research institute, in which Juan Valcárcel leads a group focusing on studies of alternative pre-mRNA splicing, the molecular mechanisms of its regulation and their alterations in cancer.
iMM is a leading Portuguese research institute nurturing innovative ideas in basic, clinical and translational Biomedical Research. The Carmo-Fonseca lab studies RNA splicing using a combination of cell imaging and genome-wide approaches.
At the Amsterdam UMC Cancer Immunotherapy and Immune Monitoring Lab, Prof Tanja de Gruijl’s and Prof. Hans van der Vliet’s combined research efforts range from preclinical topics to immune monitoring of Phase I-III clinical trials and include topics like the immune potentiation of tumour-draining lymph nodes and the tumour microenvironment, immunological arming of oncolytic adenoviruses, and VHH-mediated targeting of (NK)T-cell subsets. They contribute expertise on immune suppression, TME composition and modulation, and VHH technology.
Erez Levanon’s lab studies the dynamics of genetic information, and how it affects evolution, behaviour, and disease. Specifically, they develop technology and algorithms to uncover the full extent of A-to-I RNA editing in human and animal models. BIU contributes expertise in genomics, computational biology, RNA editing and splicing for neo-antigens.
Immunyx pioneers new approaches to immune modulation using targeted nanoparticles to change the function of neutrophils. In this project, they will work on drug delivery of targeted nanoparticles which deliver payloads to immune cells.
Merck is a biopharmaceutical company that will contribute in two main fields:
- Development of lipids and polymer carrier systems with targeting capacity.
- Selection and development of therapeutic antibodies against splice variants of proteins that will be identified in the project and may be efficient to treat cancer patient by CARs or therapeutics antibodies.
Gsap is an international consulting firm for healthcare companies, providing end to end services throughout the life cycle of medical products. Gsap contributes unique expertise in regulation of advanced cell and gene therapy products, as well as regulation of Biologics, such as proteins, Abs and vaccines. Gsap links the project’s scientific efforts to regulation requirements towards future deployment.