# CD25-Targeted Aptamer–Drug Conjugate for the Treatment of CD25-Expressing Hematological Malignancies

## TL;DR

A new drug-aptamer conjugate targeting CD25 shows promise in treating blood cancers by killing cancer cells and reducing immune suppression.

## Contribution

A CD25-targeted aptamer–drug conjugate with high specificity and efficacy in preclinical models of hematological malignancies.

## Key findings

- The CD25 aptamer showed high affinity and selective IL-2 signaling inhibition in CD25high cells.
- CD25-ApDC induced apoptosis and G2/M arrest in CD25-positive cancer cells without affecting CD25-negative cells.
- In vivo, CD25-ApDC achieved complete tumor remission and outperformed conventional therapies in some aspects.

## Abstract

Background: CD25, the α-chain of the interleukin-2 (IL-2) receptor, is highly expressed on malignant cells and tumor-infiltrating regulatory T-cells (Tregs) in hematologic malignancies, making it an attractive therapeutic target for tumor elimination and immunomodulation. Methods: We developed a CD25-specific aptamer–drug conjugate (CD25-ApDC) by linking a CD25 aptamer to monomethyl auristatin E via a cathepsin B-cleavable Val-Cit linker. Results: The aptamer exhibited high affinity for CD25 (Kd = 16.4 ± 0.29 nM), rapid receptor-mediated uptake (half-time = 9.6 min), and selective inhibition of IL-2 signaling in CD25high cells, with no activity in CD25low cells. In vitro, CD25-ApDC induced selective cytotoxicity, confirmed by apoptosis and G2/M arrest in CD25-positive cancer cells while having no effect on CD25-negative cells. Co-culture studies confirmed selective depletion of CD25high Treg-like cells, suggesting potential to relieve immune suppression within the tumor microenvironment. In vivo, CD25-ApDC achieved complete tumor remission in xenograft and disseminated models with optimized dosing, showing efficacy and tolerability comparable to Brentuximab vedotin. Increasing drug-to-aptamer ratios further enhanced outcomes, supporting flexible dosing strategies. Conclusions: These findings highlight CD25-ApDC as a promising therapeutic modality for hematologic malignancies, offering advantages in specificity, tissue penetration, and manufacturability over conventional antibody-based therapies.