Advancement of CART-Cell Therapy (Chimeric Antigen Receptor T-cell Therapy) using CRISPR/Cas9 isa major topic that I feel Biologist should work on over the next decade. Thisis so as cancer still remains as one of the most life-threatening diseases withminimal to no cure at late stages, taking the lives of many. More focus hasbeen placed in Immunotherapy in recent years as it causes less harm to the bodydue to the lesser side effects it produces as compared to chemotherapy. This isso as it utilizes the body’s own immune system to fight cancer. Immunotherapyis also more specific as it targets only the cancer cells(apart fromnon-specific cancer immunotherapies) whereas chemotherapy attacks cells undergoingcell division.
This means that normal cells undergoing cell division are alsokilled to a certain extent as well, making the side effects of chemotherapy farmore adverse. A major breakthrough in the field ofimmunotherapy would be the CAR T-Cell Therapy whereby patient’s T Cells aretaken out, modified and mass produced in the lab before infusing them back intothe patient’s body to attack on cancerous cells that harbours the targetedantigens on their surface. Many patients treated with this form of therapyshowed a high success rate and mostly, have complete remission thus far. However, since autologous T cells are utilized in CAR T-Cell Therapy, it is highly expensive andtime consuming to optimize such individualised treatments.
Hence, using T cellsfrom allogenic sources would be a more rational option as it can be useduniversally as an off-the-shelf product, so as to cut cost and save time. Theproblem with using allogenic T cells is that it causes immune rejection due to recognitionof foreign antigens by the immune system. CRISPR/Cas9, a highlyprecise genome editing technology could be used to solve this problem by editingthe genes of CAR T, making their expression of TCR(T Cell Receptor) and HLA(Human leukocyte antigen) deficient,thereby reducing immune rejection.
On top of that, CRISPR/Cas9 can be used toimprove the functionality of CAR T Cellssuch as by increasing their specificity towards certain cancer antigens or eliminatingtheir expression of PD1(Programmed celldeath protein 1) receptors.