Scientific Context of the Project
Immunotherapy using chimeric antigen receptor (CAR)-engineered lymphocytes has shown impressive results in leukemia. However, for solid tumors such as colorectal cancer (CRC), new preclinical models are needed that allow to test CAR-mediated cytotoxicity in a tissue-like environment. Patient-derived cancer organoids (PDCOs) are derived with high success rate from cancer cells of individualized patients. Studies have also shown that PDCOs can recapitulate the biological characteristics of primary tumors including histological complexity and genetic heterogeneity of cancer. When combined with immune cells and fibroblasts, tumor organoids become models for the cancer microenvironment enabling immune-oncology applications. The project will focus to develop an innovative organ-on-a-chip platform combining micro vascularized microfluidic system with patient derived cancer organoid to visualize immune cell (T or NK)-tumor interactions as well as measurements of immune cell cytotoxicity against tumor (and normal-matched) organoids for cancer. So, the organoid based CAR screening platform, named oCARs will offer opportunities in preclinical development and validation of cancer immunotherapy as well as to predict individual patient response to immunotherapy. The project will be led by Izmir Biomedicine and Genome Center (İBG) (https://www.ibg.edu.tr/research-programs/groups/erdal-lab/) and will be performed in collaboration with research group leaders from Faculty of Bioengineering and from Izmir Institute of Technology, Faculty of Science, Department of Molecular Biology and Genetics. Moreover, XNK Therapeutics, Sweden and Villanova's Center for Cellular Engineering, USA will be the international industry partner and secondment of the project.
Innovative Aspects of the Project
Patient derived cancer organoids (PDCOs) have many potential uses to predict personalized chemotherapy responses guiding therapy. Besides conventional chemotherapies, Chimeric antigen receptor (CAR) T-cell therapy is a way to get immune cells called T cells to fight cancer by changing them in the lab so they can find and destroy cancer cells. There have been several CAR T-cell agents approved by the FDA to treat hematologic malignancies. However, this type of therapy has not seen the light of victory in the fight against solid tumors because of various restricting caveats including heterogeneous tumor antigen expression and the immunosuppressive tumor microenvironments (TME) that negatively affect the tumor-site accessibility, infiltration, stimulation, activation, and persistence of CAR-Ts.
oCARs platform will have novelty with having microvascularied channels to mimic a physiologically relevant transport system to deliver candidate CAR-Ts as well as co-culture with other immune cells to recapitulate TME.
Research Environment and Infrastructure
Izmir Biomedicine and Genome Center (IBG) (https://www.ibg.edu.tr) has effectively started to operate in January 2018 as the first Center of Excellence of Turkiye. The mission of IBG is to develop innovative technologies and products for prevention, diagnosis and treatment of diseases using basic research in life sciences as a driving force. Located within the Dokuz Eylül University (DEU) health campus, IBG houses NEVCELL-Cell Therapy Unit with cGMP facility accredited by Ministry of Health of Turkiye, Drug Analysis and Control Lab. accredited by OECD, vivarium for rodent and zebrafish and Biobank for clinical samples governing by BBMRI as well as 32 research team under basic and translational research program, technological research program and industrial R&D program. The Center has core facilities including imaging, histopathology, bioinformatics, cell cultures,...,which are also open for the use of all public and private sector institutions in Turkiye. IBG is the largest and one of the well-equipped research infrastructures in Turkiye in the field of life sciences. IBG research teams are focused in the fields of cancer, rare diseases, genomics, epigenetics, stem cells and regeneration, immunology and infectious diseases, neuroscience and bioengineering. In addition to these, international conferences and symposiums are held every year, as well as comprehensive training activities such as courses, workshops, summer schools and seminars.
Under partnership of IBG, Dokuz Eylul University Izmir International Biomedicine and Genome Institute provides the international graduate programs in ‘Molecular Biology and Genetics’ (MSc and Ph.D.) and students conduct their research in IBG labs under supervision of research group leader.
oCARs (Organoid based CAR screening)
Prof. Esra Erdal (IBG)
Prof. Mayda Gürsel (IBG)
Prof. Devrim Pesen Okvur (IZTECH)
Dokuz Eylül University, Izmir International Biomedicine and Genome Institute, Dokuz Eylul University Health Campus, Balcova/İzmir
Dokuz Eylül University, Izmir International Biomedicine and Genome Institute
PhD in Molecular Biology and Genetics
Villanova University, Center for Cellular Engineering, Villanova, USA
XNK Therapeutics (SE) and Istanbul Health Industry Cluster (ISEK)