Cancers, Vol. 11, Pages 1266: Glycan-Modified Melanoma-Derived Apoptotic Extracellular Vesicles as Antigen Source for Anti-Tumor Vaccination

In this study we generated tumor-derived apoptotic extracellular vesicles (ApoEVs), which are potentially an abundant source of tumor-specific neo-antigens and other tumor-associated antigens (TAAs), and which can be manipulated to express DC-targeting ligands for efficient antigen delivery. Our data demonstrates that by specifically modifying the glycocalyx of tumor cells, high-mannose glycans can be expressed on their cell surface and on extracellular vesicles derived after the induction of apoptosis. High-mannose glycans are the natural ligands of dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), a dendritic cell associated C-type lectin receptor (CLR), which has the ability to efficiently internalize its cargo and direct it to both major histocompatibility complex (MHC)-I and MHC-II pathways for the induction of CD8+ and CD4+ T cell responses, respectively. Compared to unmodified ApoEVs, ApoEVs carrying DC-SIGN ligands are internalized to a higher extent, resulting in enhanced priming of tumor-specific CD8+ T cells. This approach thus presents a promising vaccination strategy in support of T cell-based immunotherapy of cancer.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research

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In this study, we modeled an alternative strategy to amplify tumor antigen-specific TCR transgenic CD8+ T cells through limited application of a long-acting IL-2 fusion protein, mIL-2/mCD25, which selectively targets the high-affinity IL-2R. Here, mice were vaccinated with a tumor antigen and high-dose mIL-2/mCD25 was applied to coincide with the induction of the high affinity IL-2R on tumor-specific T cells. A single high dose of mIL-2/mCD25, but not an equivalent amount of IL-2, amplified the frequency and function of tumor-reactive CD8+ T effector (Teff) and memory cells. These mIL-2/mCD25-dependent effects relied on di...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
A research team at Oslo University Hospital in Norway has opened a mesothelioma clinical trial using the novel UV1 cancer vaccine alongside a promising immunotherapy combination. UV1 is a peptide-based vaccine designed to induce a specific T-cell response and increase the effectiveness of the immunotherapy drugs. This is the first time UV1 will be studied with mesothelioma cancer, but it already has shown safety and signs of efficacy when used on malignant melanoma, prostate cancer and lung cancer in studies worldwide. It will be used with the immunotherapy combination of nivolumab and ipilimumab, also known by brand names...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
Abstract Tumor neoantigen has a high degree of immunogenicity. As one of the emerging methods of tumor immunotherapy, the vaccine developed against it has served to clinical trials of various solid tumors, especially in the treatment of melanoma. Currently, a variety of immunotherapy methods have been applied to the treatment of the tumor. However, other therapeutic methods have the disadvantages of low specificity and prominent side effects. Treatments require tumor antigen with higher immunogenicity as the target of immune attack. This review will recommend the identification of neoantigen, the influencing facto...
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - Category: Drugs & Pharmacology Authors: Tags: Biomed Pharmacother Source Type: research
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Source: International Journal of Cardiology - Category: Cardiology Authors: Source Type: research
Abstract Brain metastasis (BM) is associated with a poor prognosis, with the typical overall survival rate ranging from weeks to months in the absence of treatment. Although the concept of immune privilege in the central nervous system has eroded over time, the advent of immunotherapy has opened a new set of potential therapeutic options for patients with BM. Recently, immunotherapy has been demonstrated to confer survival advantages to patients with multiple malignancies commonly associated with BMs. Data from a number of clinical trials have demonstrated that immune checkpoint inhibitors are effective for patien...
Source: International Journal of Oncology - Category: Cancer & Oncology Authors: Tags: Int J Oncol Source Type: research
Conclusion: Our research revealed the important role of LIT-induced neutrophil infiltration on the in situ whole-cell vaccine-elicited antitumor immune response and long-term T cell immune memory.
Source: Theranostics - Category: Molecular Biology Authors: Tags: Research Paper Source Type: research
aff Immunotherapy encompasses a wide range of therapies to engage the immune system to target malignancies. In recent years, immunotherapy has made a major impact on treatment of metastatic cancer and has altered standard of care for many tumor types. However, predicting and understanding responses across tumor types has been challenging. While some metastatic cancers have shown dramatic responses to immunotherapy, such as melanoma, lung cancer, and renal cell carcinoma, prostate cancer has generally failed to show a significant response. However, small series of prostate cancer patients have shown impressive responses...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Abstract In a relatively short period of time, treatment strategies for metastatic melanoma have radically changed leading to an unprecedented improvement in patient survival. In this period, immunotherapy options have evolved from cytokine‑based approaches to antibody‑mediated inhibition of immune checkpoints, cancer vaccines and pharmacological modulation of the melanoma microenvironment. Combination of immunotherapy strategies and the association of immune checkpoint inhibitors (ICIs) with BRAF V600 targeted therapy show encouraging results. The future of drug development in this field is promising. Th...
Source: International Journal of Oncology - Category: Cancer & Oncology Authors: Tags: Int J Oncol Source Type: research
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Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
In this study, we investigated the anti-tumor efficacy of pAc/emm55 in a B16 murine melanoma model. Intralesional (IL) injections of pAc/emm55 significantly delayed tumor growth compared to the pAc/Empty group. There was a significant increase in the CD8+ T cells infiltrating into the tumors after pAc/emm55 treatment compared to the control group. In addition, we observed that IL injection of pAc/emm55 increased antigen-specific T cell infiltration into tumors. Depletion of CD4+ or CD8+ T cells abrogated the anti-tumor effect of pAc/emm55. Combination treatment of IL injection of pAc/emm55 with anti-PD-1 antibody significa...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
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