Enhanced Cell Therapy by Non-genetic Methods: Showing Huge Pote

  • Cell therapy is a novel disease treatment technology that has emerged as a therapeutic strategy for cancer diseases in recent years. It is a minimally invasive procedure, which aims to repair the diseased state of the tissue or organ to its original state by transplanting human cells. Cell therapies are designed to improve the immune system's ability to fight cancer. Some cell therapies have been successfully used for treating cancers. The oldest example is the bone marrow transplant, which is routinely used in medicine to effectively treat certain diseases of the blood and immune system, such as leukemia, lymphoma and myeloma. However, cell transplant therapies still face problems such as low cell survival rate, low level of cell integration at the transplantation site, and difficulty in retaining injected cells in the targeted focal region.


    Various chemical and materials science strategies are being developed to improve the function of therapeutic cells. Currently, scientists are using new molecules, artificial receptors, and multifunctional nanomaterials to engineer the surface of therapeutic cells, aiming to synthetically endow donor cells with new properties and functions. These novel strategies have brought significant improvement in cell survival and functional integration, leading to better therapeutic outcomes after cell transplantation.


    Cell surface modification has been generally achieved by two major methods: genetic engineering and non-genetic engineering. Genetic engineering, the most advanced cell surface modification technique, has opened up new avenues to enable existing cells to obtain specific therapeutic functions. Although genetic modification is a powerful tool, its applicability is limited by the permanent modification of cells. There is a considerable body of evidence indicating that genetic engineering does not apply to all types of cells, especially stem cells and slowly dividing cells. In comparison to genetic engineering techniques, non-genetic engineering strategies have unique advantages in disease therapy, and are complementary to existing gene-based cell engineering approaches, such as providing more reversible modifications to control cellular functions.


    Functional biomaterials, such as lipids, cationic polymers, polypeptides, genetic materials, and nanoparticles, have high gene-loading capacity and are used to endow specific functions to cells through non-genetic cell surface engineering. In particular, engineered nanomaterials hold significant promise in improving the accuracy of disease diagnosis and the specificity of treatment. In recent years, the development of nanoparticles has expanded into a broad range of clinical applications, especially in cell therapy.


    Adoptive T-cell therapy, a type of immunotherapy, has become a revolutionary approach for the treatment of cancer, especially in some hematologic malignancies with great clinical success. However, the efficacy of adoptive T cell therapy in solid tumors is restricted. Especially in tumors of the central nervous system (CNS), T cell therapy is often limited by the difficulty of intratumoral delivery, poor T cell specificity or activation, and intratumoral T cell dysfunction caused by immunosuppressive tumor microenvironments (TMEs). Recently, scientists at the University of George Washington demonstrated that nanoparticles may have the potential to overcome the limitations of T cell therapy, because they can be designed to activate T cells ex vivo prior to adoptive transfer and conjugated to T cells for enhanced function.


    This finding suggests that nanotechnology could be the key to solving many issues associated with treating CNS tumors with T cell therapy. In addition, the nanotechnology for enhanced cell therapy may have promising potential for other tumor-related diseases given their ability to penetrate anatomical barriers, encapsulate or immobilize therapeutic cargo, and specifically target tumor cells.