Protein catenation potentiates antitumor activity of malaria VAR2CSA navigation CAR-T cells in a mouse model of hematological malignancies.

ABSTRACT:

Background

While CD19-targeting chimeric antigen receptor T-cell (CAR-T) therapies have shown efficacy in B-cell hematological malignancies, treatment of antigen-negative or relapsed tumors remains challenging. The recombinant malaria protein VAR2CSA (rVAR2) binds specifically to placental-like chondroitin sulfate A (pl-CSA), which is expressed on many cancer types, enabling its use in various tumor-targeting platforms. However, rVAR2-based CAR-T strategies are limited by poor protein thermostability, short serum half-life, and safety concerns related to irreversible CAR activation. To address these limitations, we developed a navigable CAR-T cell system that uses an rVAR2-based navigator to direct CAR-T cells to pl-CSA⁺ tumors.

Methods

We overexpres

SUBMITTER: Hu W 

PROVIDER: S-EPMC12636975 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature