Enhancing Tumor Immunotherapy by Multivalent Anti‐PD‐L1 Nanobody Assembled via Ferritin Nanocage

• Published in: Advanced science Vol. 11; no. 20; pp. e2308248 - n/a
• Main Authors: Liu, Manman, Jin, Duo, Yu, Wenxin, Yu, Jiaji, Cao, Kaiming, Cheng, Junjie, Zheng, Xiaohu, Wang, Andrew, Liu, Yangzhong
• Format: Journal Article
• Language: English
• Published: Germany John Wiley & Sons, Inc 01.05.2024; John Wiley and Sons Inc; Wiley
• Subjects: Animals; Antibodies; B7-H1 Antigen - antagonists & inhibitors; B7-H1 Antigen - immunology; Cancer; Cell Line, Tumor; Dendritic cells; Disease Models, Animal; ferritin; Ferritins - immunology; Humans; Immunotherapy; Immunotherapy - methods; Indocyanine Green; Lasers; Mice; Microscopy; multivalent nanobody; Neoplasms - immunology; Neoplasms - therapy; PD‐L1; Single-Domain Antibodies - immunology; Single-Domain Antibodies - pharmacology; Spectrum analysis; Tumors; ferritin; multivalent nanobody; immunotherapy; PD‐L1
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202308248

Increasing immunotherapy response rate and durability can lead to significant improvements in cancer care. To address this challenge, a novel multivalent immune checkpoint therapeutic platform is constructed through site‐specific ligation of anti‐PD‐L1 nanobody (Nb) on ferritin (Ftn) nanocage. Nb‐Ftn blocks PD‐1/PD‐L1 interaction and downregulates PD‐L1 levels via endocytosis‐induced degradation. In addition, the cage structure of Ftn allows encapsulation of indocyanine green (ICG), an FDA‐approved dye. Photothermal treatment with Nb‐Ftn@ICG induces immunogenic death of tumor cells, which improves systemic immune response via maturation of dendritic cells and enhanced infiltration of T cells. Moreover, Nb‐Ftn encapsulation significantly enhances cellular uptake, tumor accumulation and retention of ICG. In vivo assays showed that this nanoplatform ablates the primary tumor, suppresses abscopal tumors and inhibits tumor metastasis, leading to a prolonged survival rate. This work presents a novel strategy for improving cancer immunotherapy using multivalent nanobody‐ferritin conjugates as immunological targeting and enhancing carriers. A multivalent PD‐L1 nanobody (Nb) is constructed via assembly of ferritin nanocage (Ftn). With encapsulation of photosensitizer and photothermal therapy, the Nb‐Ftn conjugate significantly enhances the immunotherapeutic response via DC maturation and enhanced T‐cell infiltration, resulting in efficient ablation of primary tumor, inhibition of distal tumor and suppression of metastasis, leading to a prolonged survival rate.