Using with the vaccine approaches that use as a starting point, we have moved increasingly deeper into an RNA technology that is becoming increasingly important in biomedicine, namely CRISPR genome editing. Thus far in this series, we have discussed CRISPR editing of genes in the context of diseases hemoglobin, notably two diseases —beta and — because those are where clinical testing is most advanced. But in this post, we will now take a look at another application of CRISPR editing in medicine, the editing of special cells called T lymphocytes, essentially to program them to seek out particular disease cells, such as cancer cells, in order to destroy them.
For several years now, biomedical researchers have been utilizing T-lymphocytes —immune cells— from humans, cells that normally can find disease causing agents, including cancer cells, and either destroy them or summon other immune cells to destroy them, depending on which type of T cells are used. Essentially, the strategy has been to weaponize T lymphocytes (also called T cells, since effectively they’re being transformed into a kind of cellular guided missile. What has particular promise, and what you may find fascinating, is that CRISPR technology is now being used to modify such T lymphocytes more easily and make them still more effective. Generally, the process has required T lymphocytes from the patients who needs the therapy, but as noted in previous articles, CRISPR has enjoyed a handful of upgrades, applied in specialized ways to different diseases.
Before taking a look at such specialized applications, let’s go through a brief overview on T lymphocytes and the immune system to which the belong. Lymphocytes are a category of white blood cells, which are the cells in your blood that are not red blood cells, the cells that carry oxygen and carbon dioxide between your body tissues and lungs and which constitute most of the cellular component of blood. Among lymphocytes, there are T lymphocytes (T cells) and B lymphocytes (B cells), and, as you can imagine there also are many different subtypes of each. B cells include plasma cells, the cells the make the antibodies that you have been hearing about so much in the contest of COVID-19 immunity and COVID-19 vaccines. As for the T cells, one type of T cell, for instance, is called a natural killer (NK) T lymphocyte, or just NK cell.
Genetic modification of NK cells can produce one type of these guided missile-like altered T cells known as a chimeric antigen receptor T cell, or CAR-T cell. The term chimeric refers to a protein that has been created by fusing smaller molecules of certain types that we don’t usually find together in nature. Equipping NK cells with such a CAR that has been engineered to connect a particular molecule allows the CAR-T cell to attach itself to any selected cell by attaching to a molecule that is particular to that target cell. If a certain type of leukemia cell has a particular molecule on its surface, for instance, a particular CAR-T cell can be designed to find and attach to such a leukemia cell. Once attached, the CAR-T cell unloads its weaponry, destroying the target cell.
Among immune therapy treatments that have reached the point of clinical trials, CAR-T cells have been used successfully in patients suffering from certain types of leukemia and certain types of lymphoma, the latter encompassing cancers that occur in cells of the lymphatic system, which is related to the immune system.
The value of CRISPR is that it enables the the creation of CAR-T cells and other types of guided missile T lymphocytes that function better, plus CRISPR is allowing such guided missile cells to be produced as a kind of off-the-shelf treatment, as opposed to treatment that has to be created specially for each patient. There are numerous innovations of CRISPR in the works showing promise. One such innovation that is particularly interesting involves a novel type of molecule that brings the CAS protein where it needs to go. Recall from earlier posts in this series that a CAS protein is a component of a CRISPR system that does the actual editing, and that the CAS has to be guided to a particular site on the DNA of the cell that is to be modified genetically. Generally in CRISPR, the guide is a strand of RNA, but this novel CRISPR application to the creation of CAR-T cells, in place of RNA uses hybrid of RNA and DNA, which is improving the CAR-T cells. This is merely one of many innovations of CRISPR that are in the works, even just in connection with CAR-T cells, which themselves are being studied, not only against lymphoma and leukemia, but even against solid cancers.