Targeting CD276 with Adapter-CAR T-cells provides a novel therapeutic strategy in small cell lung cancer and prevents CD276-dependent fratricide.

ABSTRACT:

Background

Survival rates in Small Cell Lung Cancer (SCLC) remain dismal, posing a huge medical need for novel therapies. T-cells, engineered to express chimeric antigen receptors (CAR-T) have demonstrated clinical activity against a variety of haematological malignancies. Yet, efficacy against solid tumour entities remains limited.

Methods

In this study, we investigated the expression of CD276 (B7-H3), an immune checkpoint molecule and promising target antigen for CAR-T therapy in SCLC, at the RNA and protein level. We further developed novel Fab-based adapter molecules (AM) targeting CD276 and optimized our previously established modular Adapter CAR-T (AdCAR-T) platform as well as AM dosing schemes.

Results

CD276 is broadly expressed across SCLC subtypes, representi

SUBMITTER: Kristmann B 

PROVIDER: S-EPMC12305915 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature