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Pharmaceutical company Merck and Hadassah University Hospital in Jerusalem launched CanceRNA, which aims to use messenger-RNA technology to treat cancer. CanceRNA,  a global consortium that will apply RNA-based therapeutics to successfully unlock anti-cancer immune responses, is being led by Professors at the Hebrew University of Jerusalem and The Hadassah Cancer Research Institute (HCRI) at the Hadassah University Medical Center.

While RNA-based therapies, namely mRNA vaccines, shined during the pandemic and saved millions of lives, they have yet to be successfully tested in cancer therapies. This three-year project comprises multi-disciplinary activities to assess in-vitro and in-vivo validation, bioinformatics, delivery, and safety based on new and effective modalities of immunotherapy for cancer treatment.

Cancers that were completely untreatable (such as metastatic melanoma) are showing dramatic positive responses to immunotherapy. Nevertheless, the huge promise of this treatment is diminished by the fact that only a limited percentage of patients are experiencing durable benefits from this new approach. For most patients, current immunotherapy modalities cannot prolong lifespan in a significant way and definitely cannot achieve a “cure”.

The major goal will be to modulate RNA processing in order to enhance and broaden the impact of immunotherapy in the combat against cancer. By using RNA-processing modifiers and conducting cutting-edge sequencing and bioinformatic analyses, a new armamentarium of RNA-based tools will hopefully be developed to turn immune-resistant tumors into treatment-sensitive tumors.

The CanceRNA team of researchers and scientists will be harnessing the modulation of RNA processing to enhance the accessibility and immune susceptibility of the tumor and its microenvironment, while working to enhance the activity of the immune system by retargeting immune effector cells, modulating RNA splicing of key immune receptors and developing personalized mRNA cancer vaccines.

The CanceRNA consortium kicked off with a workshop in Jerusalem this September to plan, collaborate and advance the aims of this groundbreaking international consortium to impact the future of cancer treatment. The CanceRNA consortium is funded by the European Union. The CanceRNA team, led by Professor Michal Lotem, MD, Head of HCRI, the Center for Melanoma and Cancer Immunotherapy, and Prof. Rotem Karni Department Chair at Biochemistry and Molecular Biology, Hebrew University-Hadassah Medical School, will focus on two main goals.

  1.  The modulation of RNA processing to increase the immunogenicity of “cold” cancers which lack genomic mutations, to exploit abnormal transcripts and evoke immune response;
  2. Enhancing the activity of the immune system by retargeting immune effector cells, modulating RNA splicing of key immune receptors, and developing personalized mRNA vaccines.

This multi-disciplined team is composed of international leaders in the fields of RNA research, clinicians, and biotech-pharma experts in RNA processing, RNA drug design and delivery, biocomputing, and immuno-oncology:

  • Wolf Prize Laureate Prof. Lynne Maquat, the University of Rochester;
  • Prof. Maria Carmo Fonseca, the University of Lisbon;
  • Prof. Juan Valcarcel, the Center for Genomic Regulation in Barcelona;
  • Prof. Tanja DeGruijl, the University of Amsterdam;
  • Prof. Niels Schaft, the University of Erlangen;
  • Erez Levanon, Bar Ilan University;
  • Seth Salpeter, Immunyx;
  • Pablo Menendez, Jose Carreras Leukemia Institute in Spain; Evelien Smits of the University of Brussels;
  • Regine Shevach, Managing Director, Merck Resech Activities in Israel,
  • Simon Geissler, Director, Healthcare Business of Merck
  • Daniel Helman, Project Leader, Merck Serono.

Also involved is Immunyx Pharma, a Jerusalem biotech start-up company employing experts in the field of cancer immunology and nanoparticle delivery. Immunyx Pharma is pioneering new approaches to immune modulation using targeted nanoparticles to change the function of neutrophils. The team has published several high-impact papers on the role of immune cell polarization in cancer response and has several key opinion leaders who have brought 6 nanoparticle drugs to clinical trials. In total the team has published over 50 papers on cancer immunology and nanoparticle delivery.

CanceRNA will initially focus on two cancer types, acute myeloid leukemia, relevant for pediatric cancer, and uveal melanoma, both of which harbor splicing factor mutations and that are generally refractory to immunotherapy,” said Professor Lotem. “Our hope is to utilize RNA-based therapeutics to overcome what until now, have been key barriers to successful anti-cancer immune responses. ”

CanceRNA was formed given that cancers can be made immunogenic by ‘fixating’ defective/altered RNA products, to be translated into abnormal proteins that represent neo-antigens without leaving genomic footprints. Recently developed RNA oligonucleotides and mRNAs with improved chemistry and delivery will be fundamental to this task. Furthermore, immune effector cells can be improved by altering their immune-modulatory receptors or by retargeting them to the tumor via engineered CARs or TCRs using mRNA, which allows a safer and faster transition to early clinical trials. An integral part of the scheme is the utility of delivery methods that protect oligonucleotides and mRNAs from degradation and stabilize the molecule while targeting the payload by virtue of the nanoparticles to the recipient tissue or cells.

“The combination of experts from all over Europe in the fields of RNA biology, immunology, bioinformatics and drug transport will propel the development of the next generation of immunotherapy cancer treatments,” added co-CanceRNA leader, Professor Rotem Karni, Chair of the Biochemistry and Molecular Biology Department at the Hebrew University-Hadassah Medical School.

“In the past, projects usually happened within the same industry,” Regine Shevach, Managing Director, Merck Research Activities in Israel said. “Today, however, things have changed, and often we need multidisciplinary collaborations. Some patients need better treatments, and hospitals, academia and companies team up to find the best solution. Sometimes, in order to bring about change, you have to calculate the risks. I’m very proud of my company for accepting to be part of this consortium. I’m sure this project will produce the results we are hoping for, but no matter what, we will learn a lot along the way.”

The CancerRNA Consortium Advisory board has the following scientists:

  • Adrian Krainer, PhD. St. Giles Foundation Professor; Cancer Center Deputy Director of Research; Cold Spring Harbor Laboratory. Wolf prize laureate;
  • 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;
  • Nir Hacohen, PhD. Director of the Center for Cancer Immunology at Massachusetts General Hospitals Founding member Board Institute of MIT and Harvard RNAi Consortium; Co-director of the Broad Cell Circuits Program and NHGRI Center for Cell Circuits;
  • 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;
  • Ron Weiss, PhD., Professor of Biological Engineering, Massachusetts Institute of Technology;
  • Steven A. Rosenberg, MD., PHD., Chief, Surgery Branch, National Cancer Institute, NIH;

Visit www.cancerna.info, for more information on: CanceRNA.

About CanceRNA

CanceRNA aims to impact the future of cancer treatment by developing and validating novel RNA-based therapeutics. This three-year project comprises multi-disciplinary activities to assess in-vitro and in-vivo validation, bioinformatics, delivery, and safety based on new and effective modalities of immunotherapy for cancer treatment. The CanceRNA team of researchers and scientists will be harnessing the modulation of RNA processing to enhance the accessibility and immune susceptibility of the tumor and its microenvironment, while working to enhance the activity of the immune system by retargeting immune effector cells, modulating RNA splicing of key immune receptors and developing personalized mRNA vaccines.

For more information, see www.cancerna.info.

About the Hadassah Cancer Research Institute

Hadassah Cancer Research Institute (HCRI) is a translational research arm of Hadassah Medical Organization and Sharett Cancer Center in Jerusalem. Discoveries made in HCRI labs are a driver of clinical progress and beyond. With advanced labs focused on excellence areas of research in: Immuno Oncology, Cancer Epigenetics, Early Cancer Detection, Cell Therapy, Bioinformatics, and a Biobank, our physicians and researchers are developing a multi-disciplined, multi-institution approach to discovering the next-generation treatments to fight cancer. Researchers at the Hadassah University Medical Organization in Jerusalem produced in 2012, under Good Manufacturing Practices (GMP) conditions, one of the first lines of human embryonic stem cells (hESCs) for transplantation free of animal components.

For additional information on the Hadassah Cancer Research Institute and CanceRNA, contact:
Amalia Herszkowicz, Chief Operating Officer, HCRI, Communication Officer, CanceRNA
Hadassah Cancer Research Institute (HCRI)
amaliah AT hadassah.org.il

SOURCE: Csion PRNewswire