A. Turning peptides and single chain Fv antibodies into cancer cell killers
In spite of significant progress in recent years towards the development of new targeted therapies, cancer is still a largely unmet medical need and the leading cause of death in industrialized countries. Although some cancer immunotherapy clinical trials show promise, they are complex, very expensive, require advanced medical facilities and not applicable to all patients. There is therefore a clear need for developing effective therapeutic agents that can be produced in a cost effective fashion, stored, shipped anywhere in the world and immediately available to patients with an immediate unmet medical need. To this end, we have engineered several peptide-Fc fusion proteins and single chain Fv antibody variants capable of activating innate immune effector cells such as natural killer cells and macrophages against tumour cells. The developed reagents are off-the-shelve recombinant proteins that can be used in most cancer patients.
The main objective of this project is to optimize the developed products and understand their interactions with innate immune cells.
B. Engineering better cancer vaccines
Vaccination is amongst the most efficient forms of immunotherapy. Indeed, there has been significance decline in morbidity and mortality with various infectious diseases since the use of vaccine strategies. Targeting antigens to professional antigen-presenting cells such as dendritic cells (DCs) is a concept aimed at enhancing immunity. In addition, the strategy reduces the require antigen dose substantially. At the same time, this approach ensures activation of the cells that have seen the antigen.
Notably, each step of T-cell activation by DCs is regulated by counter balancing co-stimulatory and co-inhibitory signals that fine-tune the immune response and thus protect tissue from damage when the immune system is responding to pathogens. However, in the case of cancer immunotherapy, such negative feedback mechanisms suppress the sustained activation of T cells, resulting in moderate anti-tumour immune responses. Hence, efficient inhibition of immune inhibitory pathways is crucial for the successful development of cell-based anti-tumour immunotherapy.
The main objective of this project is to target tumour antigens to DCs via newly identified DC-binding agents and simultaneously block the expression of co-inhibitory factors via RNA technology.