Author Correction: Antigen-capturing nanoparticles improve the abscopal effect and cancer immunotherapy.
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ABSTRACT:
SUBMITTER: Min Y
PROVIDER: S-EPMC9280999 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Immunotherapy holds tremendous promise for improving cancer treatment. To administer radiotherapy with immunotherapy has been shown to improve immune responses and can elicit the 'abscopal effect'. Unfortunately, response rates for this strategy remain low. Herein we report an improved cancer immunotherapy approach that utilizes antigen-capturing nanoparticles (AC-NPs). We engineered several AC-NP formulations and demonstrated that the set of protein antigens captured by each AC-NP formulation is dependent on the NP surface properties. We showed that AC-NPs deliver tumour-specific proteins to antigen-presenting cells (APCs) and significantly improve the efficacy of αPD-1 (anti-programmed cell death 1) treatment using the B16F10 melanoma model, generating up to a 20% cure rate compared with 0% without AC-NPs. Mechanistic studies revealed that AC-NPs induced an expansion of CD8+ cytotoxic T cells and increased both CD4+T/Treg and CD8+T/Treg ratios (Treg, regulatory T cells). Our work presents a novel strategy to improve cancer immunotherapy with nanotechnology.
| S-EPMC5587366 | biostudies-literature
Project description:Interest in the abscopal effect has been rekindled over the past decade with the advent of immunotherapy. Although purportedly elusive, this phenomenon is being increasingly reported. Venturing further using a multimodality approach with an array of systemic agents and unconventional modalities is direly needed. In this perspective, we describe the fundamentals of abscopal responses (ARs), explore combinations with systemic therapies that hold promise in eliciting ARs, and reconnoiter unconventional modalities that may induce ARs. Finally, we scrutinize prospective agents and modalities that exhibit preclinical ability to elicit ARs and discuss prognostic biomarkers, their limitations, and pathways of abscopal resistance for reproducibility.
| S-EPMC10116408 | biostudies-literature
Project description:In oncology, the "abscopal effect" refers to the therapeutic effect on a distant tumor resulting from the treatment of local tumor (e. g., ablation, injection, or radiation). Typically associated with radiation, the abscopal effect is thought to be mediated by a systemic antitumor immune response that is induced by two concurrent changes at the treated tumor: (1) the release of tumor antigens and (2) the exposure of damage-associated molecular patterns. Therapies that produce these changes are associated with immunogenic cell death (ICD). Some interventions have been shown to cause an abscopal effect without inducing the release of tumor antigens, suggesting that release of tumor antigens at baseline plays a significant role in mediating the abscopal effect. With tumor antigens already present, therapies that target activation of APCs alone may be sufficient to enhance the abscopal effect. Here, we discuss two therapies targeted at APC activation, TLR9 and CD40 agonists, and their use in the clinic to enhance the abscopal effect.
| S-EPMC6454083 | biostudies-literature
Project description:Immunotherapy holds tremendous promise for improving cancer treatment. Administering radiotherapy with immunotherapy has been shown to improve immune responses and can elicit an “abscopal effect”. Unfortunately, response rates for this strategy remain low. Herein, we report an improved cancer immunotherapy approach that utilizes antigen-capturing nanoparticles (AC-NPs). We engineered several AC-NPs formulations and by using a proteomic approach, we demonstrated that the set of protein antigens captured by each AC-NP formulation is dependent upon NP surface properties.
2018-10-26 | PXD006049 | Pride
Project description:PurposeTo analyze the gene mutation, immune infiltration and tumor growth of primary tumor and distant tumor under different treatment modes.Materials and methodsTwenty B16 murine melanoma cells were injected subcutaneously into the of both sides of the thigh, simulating a primary tumor and a secondary tumor impacted by the abscopal effect, respectively. They were divided into blank control group, immunotherapy group, radiotherapy group, and radiotherapy combined immunotherapy group. During this period, tumor volume was measured, and RNA sequencing was performed on tumor samples after the test. R software was used to analyze differentially expressed genes, functional enrichment, and immune infiltration.ResultsWe found that any treatment mode could cause changes in differentially expressed genes, especially the combination treatment. The different therapeutic effects might be caused by gene expression. In addition, the proportions of infiltrating immune cells in the irradiated and abscopal tumors were different. In the combination treatment group, T-cell infiltration in the irradiated site was the most obvious. In the immunotherapy group, CD8+ T-cell infiltration in the abscopal tumor site was obvious, but immunotherapy alone might have a poor prognosis. Whether the irradiated or abscopal tumor was evaluated, radiotherapy combined with anti-programmed cell death protein 1 (anti-PD-1) therapy produced the most obvious tumor control and might have a positive impact on prognosis.ConclusionCombination therapy not only improves the immune microenvironment but may also have a positive impact on prognosis.
| S-EPMC10326504 | biostudies-literature
Project description:An amendment to this paper has been published and can be accessed via a link at the top of the paper.
| S-EPMC6581903 | biostudies-other
Project description:Combined phototherapy and immunotherapy demonstrates strong potential in the treatment of metastatic cancers. An upconversion nanoparticle (UCNP) based antigen-capturing nanoplatform is designed to synergize phototherapies and immunotherapy. In particular, this nanoplatform is constructed via self-assembly of DSPE-PEG-maleimide and indocyanine green (ICG) onto UCNPs, followed by loading of the photosensitizer rose bengal (RB). ICG significantly enhances the RB-based photodynamic therapy efficiency of UCNP/ICG/RB-mal upon activation by a near-infrared (NIR) laser, simultaneously achieving selective photothermal therapy. Most importantly, tumor-derived protein antigens, arising from phototherapy-treated tumor cells, can be captured and retained in situ, due to the functionality of maleimide, which further enhance the tumor antigen uptake and presentation by antigen-presenting cells. The synergized photothermal, photodynamic, and immunological effects using light-activated UCNP/ICG/RB-mal induces a tumor-specific immune response. In the experiments, intratumoral administration of UCNP/ICG/RB-mal, followed by noninvasive irradiation with an NIR laser, destroys primary tumors and inhibits untreated distant tumors, using a poorly immunogenic, highly metastatic 4T1 mammary tumor model. With the simultaneous use of anti-CTLA-4, about 84% of the treated tumor-bearing mice achieve long-term survival and 34% of mice develop tumor-specific immunity. Overall, this antigen-capturing nanoplatform provides a promising approach for the treatment of metastatic cancers.
| S-EPMC6523374 | biostudies-literature
Project description:Despite that the impact of immune checkpoint inhibitors on malignancies treatment is unprecedented, a lack of response to these molecules is observed in several cases. Differently from melanoma and non-small cell lung cancer, where the use of immune checkpoint inhibitors results in a high efficacy, the response rate in other tumors, such as gastrointestinal cancers, breast cancer, sarcomas, and part of genitourinary cancers remains low. The first strategy evaluated to improve the response rate to immune checkpoint inhibitors is the use of predictive factors for the response such as PD-L1 expression, tumor mutational burden, and clinical features. In addition to the identification of the patients with a higher expression of immune checkpoint molecules, another approach currently under intensive investigation is the use of therapeutics in a combinatory manner with immune checkpoint inhibitors in order to obtain an enhancement of efficacy through the modification of the tumor immune microenvironment. In addition to the abscopal effect induced by radiotherapy, a lot of studies are evaluating several drugs able to improve the response rate to immune checkpoint inhibitors, including microbiota modifiers, drugs targeting co-inhibitory receptors, anti-angiogenic therapeutics, small molecules, and oncolytic viruses. In view of the rapid and extensive development of this research field, we conducted a systematic review of the literature identifying which of these drugs are closer to achieving validation in the clinical practice.
| S-EPMC6521062 | biostudies-literature
Project description:PurposeIn this study, we aimed to assess the abscopal effect (AE) after CyberKnife stereotactic body radiotherapy (SBRT) in metastatic breast cancer patients without immunotherapy.MethodsWe reviewed breast cancer patients who received SBRT with a fraction size of ≥ 6 Gy for metastatic lesions between July 2008 and December 2021. We selected patients who had at least one measurable extracranial lesion in addition to SBRT target lesions and were not treated with immunotherapy. A total of 40 SBRT cases from 34 patients were included in the analysis. The AE was defined as occurring before the overall progression of the disease, regardless of the use of systemic treatment.ResultsThe median follow-up duration was 16.4 months. Among 40 SBRT cases, the AE was observed in 10 (25.0%) with a median interval of 2.1 months. Of these lesions, 70.0% did not progress for one year. In multivariate logistic regression analysis, no change in systemic treatment after SBRT was significantly associated with an increase in the AE (odds ratio [OR] = 1.428, 95% confidence interval [CI] = 1.108 - 1.841, p = 0.009). A post-SBRT neutrophil-to-lymphocyte ratio (NLR) of < 2 marginally increased the AE (OR = 1.275, 95% CI = 0.998 - 1.629, p = 0.060). However, a high SBRT dose and large planning target volume did not (p = 0.858 and 0.152, respectively) in univariate analysis.ConclusionsOne out of four patients experienced the AE after SBRT in the absence of immunotherapy. The AE could occur more frequently when systemic treatment remains unchanged, and patients have a low NLR after SBRT.
| S-EPMC10587686 | biostudies-literature
Project description:Ionizing radiation therapy is a well-established method of eradicating locally advanced tumors. Here, we examined whether local RT enhanced the potency of an antigen-specific DNA vaccine, and we investigated the possible underlying mechanism. Using the HPV16 E6/E7+ syngeneic TC-1 tumor, we evaluated the combination of CTGF/E7 vaccination with local irradiation with regard to synergistic antigen-specific immunity and anti-tumor effects. Tumor-bearing mice treated with local RT (6 Gy twice weekly) and CTGF/E7 DNA vaccination exhibited dramatically increased numbers of E7-specific CD8+ cytotoxic T cell precursors, higher titers of anti-E7 Abs, and significantly reduced tumor size. The combination of local RT and CTGF/E7 vaccination also elicited abscopal effects on non-irradiated local subcutaneous and distant pulmonary metastatic tumors. Local irradiation induced the expression of high-mobility group box 1 protein (HMGB-1) in apoptotic tumor cells and stimulated dendritic cell (DC) maturation, consequently inducing antigen-specific immune responses. Additionally, local irradiation eventually increased the effector-to-suppressor cell ratio in the tumor microenvironment. Overall, local irradiation enhanced the antigen-specific immunity and anti-tumor effects on local and distant metastatic tumors generated by an antigen-specific DNA vaccine. These findings suggest that the combination of irradiation with antigen-specific immunotherapy is a promising new clinical strategy for cancer therapy.
| S-EPMC5835145 | biostudies-literature