drug-resistant engineered γδ t cells development

In principle, gene therapy is to introduce nucleic acid sequences into target cells to prevent or cure many diseases. The technical obstacles of this treatment method, such as the insufficient transfer of genetic material into cells, resulting in low transgene integration, and the safety problems of gene transfer method limit its use. Now, advances in all areas of gene therapy allow for the development of cell-based cancer therapies with strong immunity based on genetic engineering.

Background

In the treatment of cancer, the therapeutic role of immune cells in controlling malignant tumors has been fully established. For example, immunocompetent hosts often reject transplanted tumors, while tumors can be easily established in immunosuppressed hosts. However, intensive chemotherapy is the first-line therapy for advanced cancer patients, which often leads to non-specific cytotoxicity to adoptive transferred immunocompetent cells and hematopoietic stem cells. One strategy to combat drug-induced toxicity is to genetically modify immune cells to make them resistant.

As cell-based immunotherapy, γδ T cells have a key advantage: they can be given directly from the donor to the patient without producing graft-versus-host disease, unlike αβ T cells that require extensive gene editing to remove major histocompatibility complex (MHC) and T cell receptor (TCR) genes.