Genetic Engineering Publications - GEG Tech top picks

Until recently, most CAR-T therapies were made from the patient's own cells, but the long-term commercial viability of cell therapies of all types will rely on "allogeneic" cells, therapeutic cells mass-produced and grown from a source outside the patient. However, the recipient's immune system is likely to treat all outside cells as foreign and reject them. Immune rejection of therapeutic cells, such as CAR-T cells, mediated by antibodies, as opposed to chemical aggression initiated by them, has proven to be particularly challenging to resolve. This is a factor that hinders the development of these treatments. Researchers have therefore developed a method to catch antibodies before they bind to cells, preventing the activation of the immune response. The researchers genetically engineered three types of cells :  insulin-producing islet cells, thyroid cells and CAR-T cells, so that each type makes and displays a large number of a protein called CD64 on their surface. On these engineered cells, CD64, which tightly binds the antibodies responsible for this type of immune rejection, acted as a kind of decoy, capturing the antibodies and binding them to the engineered cell, so that they would not activate the immune cells. The new strategy is described in Nature Biotechnology.

An antibody-based conditioning agent may open the way to wider application of gene therapy with hematopoietic stem cells.

CAR T-cell therapy and antibody treatments are two types of targeted immunotherapies that have revolutionized the fields of cancer care. However, there are still significant challenges in identifying cancer cell surface proteins as targets for immunotherapies. A research group at Lund University in Sweden is well on their way as they have developed a new precision medicine technology that allows for comprehensive mapping of the entire tumor cell surface antigen landscape in patients. The method developed by the research team, "Tumor Surfaceome Mapping, TS-MAP," allows direct analysis of all accessible tumor cell surface antigens in patient tumor tissue. In a close collaboration between neurosurgery, oncology and advanced proteomics in Lund, the researchers were able to identify several tumor cell surface antigens in fresh tissue from patients with aggressive brain tumors for which there is currently no effective treatment. An important advantage of the TS-MAP technology is that it provides a complete picture of the cell surface antigens displayed on the surface of the cancer cell, as well as information about specific cell surface antigens that have a high capacity to infiltrate cancer cells, and can destroy them from within. 

In this work, the scientists have developed a novel system to convert scFvs from a phage display vector directly into IgGs without any in vitro subcloning steps. This new vector system, named pMINERVA, makes clever use of site-specific bacteriophage integrases that are expressed in Escherichia coli and intron splicing that occurs within mammalian cells.