Determining Antibody Response to CAR T Cell Therapy in SIV Infected Rhesus macaques
Human immunodeficiency virus (HIV) continues to be a global problem, despite substantial research over the past four decades. Previous treatments have been unsuccessful in eliminating HIV infection due to latent viral reservoirs, and there is still the need to find a functional cure. Preliminary work has shown that chimeric antigen receptor (CAR) T cells directed to the B cell follicle to kill simian immunodeficiency virus (SIV) infected cells is associated with decreased viral loads in Rhesus macaques. However, these engineered T cells do not persist long term in vivo. We hypothesized that persistence could be inhibited by an antibody mediated clearance of the CAR T cells. To test this hypothesis, we investigated the frequency of serum antibodies on CAR transduced PBMCs by flow cytometry. We found an IgG antibody response to the CAR construct at both early and late time points post infusion in five out of 6 treated animals. In addition to problems associated with CAR T cell persistence, an antibody response against the CAR construct makes a second infusion impossible due to potential anaphylactic reaction and other unfavorable reactions in vivo. These findings support the need for more research regarding immune responses to CAR T cell therapy before they can be considered as a functional cure for HIV.