Table 2.

Open questions concerning the clinical use of CAR-engineered T cells in the treatment of chronic hepatitis B.

(i) Does binding to individual HBV infected cells trap the anti-HBV CAR T cells locally in the liver?
(ii) To which extend are HBV-infected hepatocytes eliminated by engineered T cells?
(iii) Will the immune suppressive microenvironment silence transferred T cells?
(iv) What effect would circulating HBsAg or subviral HBV particles have on the activation of engineered T cells? Do soluble HBV particles
induce CAR mediated “on-target off-organ” T cell activation?
(v) Is HBV-specific T cell memory induced?
(vi) How can induction of anergy of engineered T cells be prevented?
(vii) Do inflammatory cytokines secreted by activated T cells attract a second wave of nonspecific inflammatory cells, and how do these
cells comodulate the anti-HBV T cell response?