Systemically administered low-affinity HER2 CAR T cells mediate antitumor efficacy without toxicity.

ABSTRACT:

Background

The paucity of tumor-specific targets for chimeric antigen receptor (CAR) T-cell therapy of solid tumors necessitates careful preclinical evaluation of the therapeutic window for candidate antigens. Human epidermal growth factor receptor 2 (HER2) is an attractive candidate for CAR T-cell therapy in humans but has the potential for eliciting on-target off-tumor toxicity. We developed an immunocompetent tumor model of CAR T-cell therapy targeting murine HER2 (mHER2) and examined the effect of CAR affinity, T-cell dose, and lymphodepletion on safety and efficacy.

Methods

Antibodies specific for mHER2 were generated, screened for affinity and specificity, tested for immunohistochemical staining of HER2 on normal tissues, and used for HER2-targeted CAR design. CAR cand

SUBMITTER: Shabaneh TB 

PROVIDER: S-EPMC11145640 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature