Framework humanization optimizes potency of anti-CD72 nanobody CAR-T cells for B-cell malignancies.

ABSTRACT:

Background

Approximately 50% of patients who receive anti-CD19 CAR-T cells relapse, and new immunotherapeutic targets are urgently needed. We recently described CD72 as a promising target in B-cell malignancies and developed nanobody-based CAR-T cells (nanoCARs) against it. This cellular therapy design is understudied compared with scFv-based CAR-T cells, but has recently become of significant interest given the first regulatory approval of a nanoCAR in multiple myeloma.

Methods

We humanized our previous nanobody framework regions, derived from llama, to generate a series of humanized anti-CD72 nanobodies. These nanobody binders were inserted into second-generation CD72 CAR-T cells and were evaluated against preclinical models of B cell acute lymphoblastic leukemia and B cel

SUBMITTER: Temple WC 

PROVIDER: S-EPMC10680002 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature