Research Fellow Nanyang Technological University Singapore, Singapore
Abstract: Cell based cancer immunotherapies are complex living drugs, which has emerged as complementary fourth pillar of cancer treatments alongside surgery, chemotherapy and radiation. However, immunotherapy benefits are mostly confined to liquid cancers and to a limited subset of solid tumor patients. Generalization of immunotherapies have failed to make an impact on gastric cancers. Monocytes and macrophages are the dominant cellular constituents, which are reprogrammed by the tumor to support their growth. However, these macrophages innately engulf cancer cells as a natural defense mechanism. We envision to leverage the potential of these powerful cancer eaters, which are also the natural inhabitants of the solid tumors. We will use our lambda-integrase genome engineering technology (LIGIT) to engineer multiple functional modules in stem cells as a renewable source of tissue macrophages. These functional modules will encompass chimeric antigen receptors (CARs) that will render tumor recognition capability to engineered stem cell derived monocytes and macrophages. Additionally, other functional modules such as brain homing, and tumor kill signals will enable passage of these robust cancer eaters to the tumor site and facilitate killing and inhibition of tumor growth. As such multi-modular functional gene assemblies can only be possible with genetic engineering tools that can integrate DNA of 10-15kb size or more. In this context LIGIT platform offers versatility to achieve such large DNA integrations for innovative cell and gene therapies. Thus, we are well poised to develop first-in-class prototype for robust cell based brain tumor immunotherapies, which can be translatable to brain metastasis and other solid tumors.
Funding Source: A*STAR (Singapore Therapeutics Development Review funding)
