Humanizing a CD19-specific VHH domain to boost CAR-T cell efficacy
Kozani PS, Kozani PS, Rahbarizadeh F Humanization of the Antigen-Recognition Domain Does Not Impinge on the Antigen-Binding, Cytokine Secretion, and Antitumor Reactivity of Humanized Nanobody-Based CD19-Redirected CAR-T Cells. Journal of Translational Medicine. 2024; (doi: 10.1186/s12967-024-05461-8).
The anti-tumor effects of CD19-targeted chimeric antigen receptor (CAR) T cells may potentially weaken following infusion due to immunogenicity of their antigen-recognition domains, but research suggests that humanizing the domains is a viable solution. With a goal toward enhancing CAR-T efficacy, investigators used in silico methods to humanize the CD19-specific nanobody known as H85. The resulting HuH85CAR-T cells yielded similar CAR expression and surface density rates, comparable secretion of interleukin-2 and other cytokines, and similar cytolytic reactivity as H85CAR-T cells that were not humanized. No negative effects were observed from humanizing HuH85; however, the study authors underscore the need for additional in vitro observation and experiments with preclinical xenograft models of CD19+ malignancies before pursuing clinical trials.