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Summary

This module will cover advanced concepts of cell-based immunotherapies for cancer, from target identification and synthetic biology for cell engineering, to their pre-clinical development and clinical translation. The module will provide the participants with unique access to the latest data from the broad ranging portfolio of chimeric antigen receptor (CAR) T cell studies taking place at GOSH and will contextualize the main clinical limitations identified and novel approaches being undertaken to refining cell-based immunotherapy strategies to reduce toxicity and prevent therapy escape.

Learning outcomes and objectivesÌý

The aim of the module is to equip students with a critical understanding of the field of cell-based immunotherapies of cancer and other immune disorders. The module will introduce basic concepts of immunology and will provide in-depth insights on immune cell engineering. The students will learn the full path from target identification, cell engineering to clinical applications that are currently being undertaken at GOSH and other world leading international centers. Most importantly, they will be able to critically recognize strengths and limitations of the presented studies and to discuss future directions being prioritized in the field.Ìý

On completion of the module students will:Ìý

• Understand the principles of cell-based immunotherapy and novel target identificationÌý

• Understand the immune system, immune cell types that can be engineered with CARs and their physiological functions and distinctive biological featuresÌý

• Be able to choose the appropriate approach to target identification and selective targeting.Ìý

• Critically think about the application of synthetic biology approaches to immune-cell engineeringÌý

• Have knowledge and understanding of pre-clinical and clinical studies carried on at ¹û¶³Ó°Ôº GOSH/¹û¶³Ó°ÔºH and other institutions, including current limitationsÌýÌý

• Be able to Identify novel approaches to overcoming the limitations identified in the current clinical trials.ÌýÌý

• Be able to identify new approaches to reduce toxicity and prevent antigen negative therapy escapeÌý

Teaching and Learning methodsÌý

The module is aimed to be highly interactive with a blend of taught lectures and interactive applied case studies, interactive activities and discussion groups, self-taught sessions, tutorial and practices (i.e. relevant database searches) and will use virtual reality applications to explore the possibilities of personalised medicine.Ìý

Selected reading list:Ìý

1. Maus, M.V., Grupp, S.A., Porter, D.L. & June, C.H. Antibody-modified T cells: CARs take the front seat for hematologic malignancies. Blood 123, 2625-2635 (2014).Ìý

2. Barrett, D.M., Grupp, S.A. & June, C.H. Chimeric Antigen Receptor- and TCR-Modified T Cells Enter Main Street and Wall Street. J Immunol 195, 755-761 (2015).Ìý

3. Kershaw, M.H., Westwood, J.A. & Darcy, P.K. Gene-engineered T cells for cancer therapy. Nat Rev Cancer 13, 525-541 (2013).Ìý

4. June, C.H., O'Connor, R.S., Kawalekar, O.U., Ghassemi, S. & Milone, M.C. CAR T cell immunotherapy for human cancer. Science 359, 1361-1365 (2018).Ìý

5. Labanieh, L., Majzner, R.G. & Mackall, C.L. Programming CAR-T cells to kill cancer. Nat Biomed Eng 2, 377-391 (2018).Ìý

6. Fesnak, A.D., June, C.H. & Levine, B.L. Engineered T cells: the promise and challenges of cancer immunotherapy. Nat Rev Cancer 16, 566-581 (2016).Ìý

7. Hunger, S.P. & Mullighan, C.G. Acute Lymphoblastic Leukemia in Children. N Engl J Med 373, 1541-1552 (2015).Ìý

8. Majzner, R.G. & Mackall, C.L. Tumor Antigen Escape from CAR T-cell Therapy. Cancer Discov 8, 1219-1226 (2018).Ìý

9. D'Ippolito, E., Schober, K., Nauerth, M. & Busch, D.H. T cell engineering for adoptive T cell therapy: safety and receptor avidity. Cancer Immunol Immunother 68, 1701-1712 (2019).Ìý