Reviewed by Lexie CornerJan 24 2025
A research team led by Professor Yaping Li from the Chinese Academy of Sciences' Shanghai Institute of Materia Medica and Professor Pengcheng Zhang of ShanghaiTech University developed a novel approach to local neoadjuvant immunotherapy, as detailed in Nature Communications.
The efficacy of immunotherapy for triple-negative breast cancer (TNBC) depends heavily on the infiltration of cytotoxic T lymphocytes (CTLs) into the tumor. Despite the approval of neoadjuvant chemotherapy and immunotherapy for advanced TNBC, treatment outcomes remain suboptimal, potentially due to systemic therapy-induced lymphatic system dysfunction and tumor activation of alternative immune checkpoints.
The researchers developed an injectable hydrogel, Abe-NF(g), composed of peptide-NLG919 prodrug nanofibers loaded with the cyclin-dependent kinase 4/6 inhibitor Abemaciclib (Abe). Following local injection, the hydrogel remained at the tumor site for at least seven days, serving as a sustained reservoir for Abe and NLG919. This approach significantly improved the drug distribution ratio between tumors and critical organs.
The prolonged tumor exposure to Abe induced immunogenic cell death, enhanced dendritic cell maturation, activated classic macrophages, and stimulated CTLs. Reduced systemic exposure minimized the occurrence of lymphopenia and hepatic toxicity.
Additionally, while Abe increased the expression of the enzyme indoleamine 2,3-dioxygenase 1 (IDO1), the sustained release of NLG919 inhibited IDO1 activity, reducing kynurenine synthesis and regulatory T-cell activation. A single injection of Abe-NF(g) enhanced CTL tumor infiltration and effector memory T cell formation, effectively reducing TNBC recurrence and pulmonary metastasis.
This study demonstrates progress in local neoadjuvant immunotherapy for TNBC, achieving improved efficacy with lower toxicity. The injectable hydrogel platform, based on prodrug fibrous nanomedicine, offers potential for combination therapies to achieve synergistic effects.
Journal Reference:
Zhu, B., et al. (2025) Injectable supramolecular hydrogel co-loading abemaciclib/NLG919 for neoadjuvant immunotherapy of triple-negative breast cancer. Nature Communications. doi.org/10.1038/s41467-025-55904-z