HIV is one of the most well know viruses of the 21st centaury, however, patients suffering from the disease still have no cure and must adhere to strict regimens of anti-viral therapies in order to simply stay alive. To address this devastating disease, researchers have identified a novel means of immunotherapy which is able to detect and destroy HIV viruses for a lifetime. Originally, researchers tried to attach an HIV specific Chimeric Antigen Receptor (CAR) to a peripheral T-helper cell in order to eliminate HIV present in the bloodstream. In the short term, the therapy was able to reduce viral load, however, because peripheral T-helper cells eventually die off, the virus was able to come back and once again reek havoc on the body. In order to ensure that CAR-T cells would continuously attack reoccurring HIV infections, the authors decided to genetically engineer hematopoietic stem cells (HSCs) to express an HIV specific CAR in conjunction with a CD4 protein when the HSC differentiated into a T-helper cell. The HSCs also expressed the HIV inhibitor C46, ensuring that any T-helper cell differentiated from a genetically modified HSC would not only identify and destroy an HIV virus, but also be impenetrable to HIV infection. In order to analyze if the engineered HSPs could induce an immune response against HIV viruses the C46CD4CAR HSCs were injected directly in juvenile pigtail macaques. The animals were then infected with Simian HIV (SHIV-C) for 24 weeks and given combination retroviral therapy (cART) for 28 weeks prior to complete cART withdrawal. The macaques treated with C46CD4CAR HSCs prior to infection showed a significantly lower HIV viral load throughout the primary infection as well as reduced drug rebound viremia compared with non-CAR controls. The treated animals also presented with a significant increase in HIV dependent anti-HIV T-helper cells in peripheral lymphoid tissues post infection compared with controls as well as a normal HSP differentiation rate through haematopoiesis throughout the 2 year study. These results, pooled together, indicate the safety, tolerability, and effectiveness of using CAR modified HSPs to treat HIV in human trials as well as treating other immunological based diseases.
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