Dataset Information

Red Blood Cell-Mimic Nanocatalyst Triggering Radical Storm to Augment Cancer Immunotherapy.

ABSTRACT: Red blood cells (RBCs) have recently emerged as promosing candidates for cancer treatment in terms of relieving tumor hypoxia and inducing oxidative damage against cancer cells, but they are still far from satisfactory due to their limited oxygen transport and reactive oxygen species generation rate in tumor tissue. Herein, artificial RBCs (designated FTP@RBCM) with radical storm production ability were developed for oncotherapy through multidimensional reactivity pathways of Fe-protoporphyrin-based hybrid metal-organic frameworks (FTPs, as the core), including photodynamic/chemodynamic-like, catalase-like and glutathione peroxidase-like activities. Meanwhile, owing to the advantages of long circulation abilities of RBCs provided by their cell membranes (RBCMs), FTP with a surface coated with RBCMs (FTP@RBCM) could enormously accumulate at tumor site to achieve remarkably enhanced therapeutic efficiency. Intriguingly, this ROS-mediated dynamic therapy was demonstrated to induce acute local inflammation and high immunogenic cancer death, which evoked a systemic antitumor immune response when combined with the newly identified T cell immunoglobulin and mucin-containing molecule 3 (Tim-3) checkpoint blockade, leading to not only effective elimination of primary tumors but also an abscopal effect of growth suppression of distant tumors. Therefore, such RBC-mimic nanocatalysts with multidimensional catalytic capacities might provide a promising new insight into synergistic cancer treatment.

SUBMITTER: Li J

PROVIDER: S-EPMC8817004 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Red Blood Cell-Mimic Nanocatalyst Triggering Radical Storm to Augment Cancer Immunotherapy.

Li Jiong J Wang Sijia S Lin Xinyi X Cao Yanbing Y Cai Zhixiong Z Wang Jing J Zhang Zhenxi Z Liu Xiaolong X Wu Ming M Yao Cuiping C

Nano-micro letters 20220205 1

Red blood cells (RBCs) have recently emerged as promosing candidates for cancer treatment in terms of relieving tumor hypoxia and inducing oxidative damage against cancer cells, but they are still far from satisfactory due to their limited oxygen transport and reactive oxygen species generation rate in tumor tissue. Herein, artificial RBCs (designated FTP@RBCM) with radical storm production ability were developed for oncotherapy through multidimensional reactivity pathways of Fe-protoporphyrin-b ...[more]

PMID: 35122163

Similar Datasets

Project description:BackgroundHead and neck squamous cell carcinoma (HNSCC) is a major cause of cancer-related morbidity and mortality worldwide. Epidermal growth factor receptor (EGFR)-targeted therapy is an attractive strategy alternative to conventional cancer treatments for HNSCC, but its efficacy remains controversial. T-cell-based immunotherapy has been proposed as a novel therapeutic approach to improve the clinical outcome for HNSCC. In this study, we report human epidermal receptor (HER) family epitopes that induced CD4 T-cell responses to HNSCC. The results provide support for a novel strategy to treat HNSCC by combining EGFR-targeted therapy with T-cell-based immunotherapy.MethodsWe evaluated the capacity of predicted CD4 T-cell peptide epitopes from EGFR to induce antitumour immune responses in vitro. In addition, EGFR inhibitors were evaluated for their ability to augment tumour MHC class II expression in HNSCC cell lines and subsequently increase T-cell recognition.ResultsAmong several predicted peptide epitopes, EGFR875-889 elicited CD4 T-cell responses that were restricted by HLA-DR4, DR15, or DR53 molecules, indicating that the peptide functions as a promiscuous T-cell epitope. The peptide-reactive T cells responded to autologous dendritic cells loaded with EGFR-expressing tumour cell lysates, indicating that these epitopes are naturally processed. In addition, the CD4 T cells were capable of directly recognising and killing HNSCC cells expressing EGFR and the appropriate HLA class II molecule. T cells reactive with the EGFR875-889 epitope could be detected in the blood of HNSCC patients. EGFR875-889-reactive CD4 T cells were also able to recognise several peptide analogues derived from homologous regions of EGFR family members, HER-2, HER-3 and c-MET. Finally, we examined the effects of EGFR tyrosine kinase inhibition or EGFR-blocking antibodies on CD4 T-cell tumour reactivity. Treatment of tumour cells with the EGFR inhibitors enhanced tumour recognition by EGFR875-889-reactive T cells presumably due to the upregulation of HLA-DR expression in the HNSCC cells.ConclusionWe identified novel CD4 T-cell EGFR epitopes and amongst these, EGFR875-889 functions as a promiscuous helper T-cell epitope that can elicit effective antitumour T-cell responses against tumours expressing HER family members and c-MET. These observations should facilitate the translation of T-cell-based immunotherapy into the clinic for the treatment of HNSCC and provide a rational basis for EGFR inhibition, immune-targeted combination therapy.

Dataset Information

Red Blood Cell-Mimic Nanocatalyst Triggering Radical Storm to Augment Cancer Immunotherapy.

Publications

Red Blood Cell-Mimic Nanocatalyst Triggering Radical Storm to Augment Cancer Immunotherapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets