GAPP APPLICATION COMPLEMENTARY INFORMATION
TITLE: Establishing Therapeutic Cord Blood derived NK cells for hard-to-treat cancers through Omics-based selection and pharmacological activators
Flow and CITE-seq Antibody Tables
List of AML cell lines
Article from the Dr Langlais’ lab demonstrating the power of using of single cell and multiomics deep characterization in the context immune responses and diseases. In this case, the use of multiomics approached on severely ill COVID-19 patients allowed for the identification of a signature predictive of progression to death, but also identified dysregulated pathways and potential FDA-approved drug to target these pathways; most are in clinical trial by other groups currently.
Article from the Dr Langlais’ lab where CITE-seq was used to characterize the severe immune defects in the first-to-be-reported IRF1 deficient patients.
Supplemental information about the research sites and project team
The Cell Therapy Lab (CTL): The CTL is center of excellence that helps support basic, translational, and clinical applications for cellular therapies. The CTL was a co-applicant in the successful CFI ExCELLirate proposal funded to help develop “point of care” cellular therapies for cancer in Canada, and that will support the implementation of our innovation into clinical trial. Dr. Pierre Laneuville is the director of the CTL, and a hemato-hematologist and Associate Investigator at the RI-MUHC. He was also director of the Dept of Hematology at McGill U. He has a long track record in clinical research and trials and will act as the lead of the main Receptor (MUHC). Dr. Laneuville has been a PI or co-PI in over 100 clinical trials and is certified by the MUHC-RI for conducting clinical trials.
Dr. Linda Peltier has been in the field of clinical trials and cellular therapy, and an international inspector for cord blood banks for the past 15 years. She established Canada's first umbilical cord blood bank while working at Hema Quebec and hence has the experience and training of working in one of the most demanding regulatory environment, that of a public blood and tissue provider. She is also a certified FACT (Federation for the Accreditation of Cellular Therapy) and regularly inspects clinical transplant programs, hematopoietic stem cells laboratories, and umbilical cord blood banks world-wide that seek certification with FACT. Dr. Peltier is also the first Canadian to receive the AABB Certified Advanced Biotherapies Professional (CAPB) certification. After establishing the Public Cord Blood Bank of Hema-Québec, she established the Human umbilical cord blood bank and the CTL at the MUHC with Dr. Pierre Laneuville. She ensures that all processes established within the CTL are compliant to GLP, GMP and Health Canada regulations, which will streamline the development of our Phase I clinical trial. The CTL aims to translate fundamental new treatments into clinical trials involving cellular therapy.
Kanyr Pharma: Kanyr Pharma Inc. was co-funded by Daniel Bouthillier and Prof. Tremblay in 2013, to advance research on cancer immunotherapy using compounds that act on phosphatases. Kanyr’s research team possesses over 15 years of experience in the PTP field and is a world-leader in the understanding of how to chemically target PTP gene family. PTPs have long been thought to be “undruggable”, but recent successes show that this is no longer the case. Kanyr has developed and acquired the rights on proprietary PTPN1/N2 inhibitors, including KQ791 that is our most potent and safe compound, that we will use in this GAPP Program. Kanyr, and its management and legal team, has decades of experience in the development of human therapies, involvement in clinical trials, and of working toward Health Canada accreditation. Dr. Daniel Bouthillier will contribute to both the Project Team and the Advisory Committee regular meetings. He will ensure the progression of the technology and contribute to the discussion on the licensing in agreement with the IP Term Sheet provided in Appendix II.
Prof. Michel L. Tremblay is the Academic Project Leader on this application. He is a Distinguished James McGill Professor and former director of the Goodman Cancer Centre (now an Institute). He is a laureate of several major prizes in Quebec and Canada. Internationally, he is recognized for his work on Protein Tyrosine Phosphatases and his contributions to cancer, diabetes, and neuroscience. He founded three companies, including Kanyr Pharma. For the last 10 years, he shared a Strauss and Aclon Foundation team grant with Dr. Laneuville. Together, they have developed an expertise in cell therapy. He has also participated as a co-applicant in CERC and CFI grants led by Dr. Langlais. Hence the Receptors and Academic leaders of this application have been working and sharing their expertise together for several years.
Prof. David Langlais is an Associate Professor in Human Genetics and Microbiology & Immunology at McGill University, and Principal Investigator at the Dahdaleh Institute of Genomic Medicine (DIGM). He is an expert in functional genomics, bioinformatics, and genome editing, including developing and applying single cell multi-omics methods for clinical projects. He collaborates on numerous local and international clinically relevant projects published in top-tier journals. He received numerous prizes for his contribution in the fields of infection and immunity, including the Seymour and Vivian Milstein Young Investigator Award from the International Cytokine & Interferon Society. Notably, Quebec Science recognized two of his research breakthroughs in the Top 10 Discoveries of the Year in 2018 and 2022.
The DIGM is at the forefront of national and international genetic and genomic initiatives. It has been the site of major operational and infrastructure investments since its foundation in 2002, maintaining its leadership. Supporting this GAPP Program, the DIGM currently operates multiple short-read sequencers (2x MiSeq, 3x NovaSeq 6000 [Illumina], DNBSEQ-G400, DNBSEQ-T7 [MGI]), together with third-generation sequencing technologies (PacBio, Nanopore). Moreover, Dr Langlais has also built a complete and streamlined single cell multiomics BCL2 lab that allow the processing and capture of human samples for single cell multiomics application. This lab is operated by HQPs expert in the field and supported by the DIGM genomics and bioinformatics core facilities for the sequencing of single cell libraries and for the basic bioinformatic samples QC and demultiplexing. Due to this unique installation and expertise, the GAPP Team is in an advantageous position to conduct the proposed multiomics research plan.
Other expert HQPs will be selected to join the team and move the GAPP project along. The team will use objective criteria in selecting candidates to ensure that the process is fair, inclusive, and equitable. This will involve using blind screening processes, structured interviews, and avoiding unconscious biases. The team will foster an inclusive culture that values and respects diversity. This may involve creating a safe and welcoming environment for all team members, promoting open communication and dialogue, and encouraging them to share their experiences and perspectives.