Progress in Neoantigen Targeted Cancer Immunotherapies

Han, Xianbo; Ma, Xuelei; Yang, Li; Wei, Yuquan; Peng, Yong; Wei, Xiawei

doi:10.3389/fcell.2020.00728

Cited by 31 publications

(26 citation statements)

References 299 publications

(329 reference statements)

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“…(4)(5)(6) The difference in MHC expression between healthy and diseased cells is small, and neoantigens are expressed at much lower levels than canonical peptides. (3)(4)(5)7) While mutated and post-translationally modified antigens were introduced concurrently and have similar reactivity (8), modified antigens are comparatively understudied. (9, 10) However, disease-associated modifications are caused by dysregulated signaling pathways that are common across different individuals, cancers, and even other diseases.…”

Section: Introductionmentioning

confidence: 99%

MHC Phosphopeptides: Promising Targets for Immunotherapy of Cancer and Other Chronic Diseases

Mahoney

Shabanowitz

Hunt

2021

Molecular & Cellular Proteomics

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Section: Introductionmentioning

confidence: 99%

MHC Phosphopeptides: Promising Targets for Immunotherapy of Cancer and Other Chronic Diseases

Mahoney

Shabanowitz

Hunt

2021

Molecular & Cellular Proteomics

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“…Tumor antigens, especially neoantigens, are key targets for anticancer immunotherapy (33)(34)(35). The local administration of CAER agents to tumor cells can lead not only to increased tumor cell death but also to the release of a larger amount of tumor antigens, including neoantigens, for antigen presentation (36)(37)(38). With our local therapy regimen, the tumors were quickly eradicated, concomitant with the infiltration of a large number of T cells.…”

Section: Discussionmentioning

confidence: 97%

A Local and Low-Dose Chemotherapy/Autophagy-Enhancing Regimen Treatment Markedly Inhibited the Growth of Established Solid Tumors Through a Systemic Antitumor Immune Response

Yuan

et al. 2021

Front. Oncol.

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Chemotherapy is one of the main options for the treatment of a variety of malignant tumors. However, the severe side effects resulting from the killing of normal proliferating cells limit the application of cancer-targeting chemotherapeutic drugs. To improve the efficacy of classic systemic chemotherapy, the local delivery of high-dose chemotherapeutic drugs was developed as a method to enhance local drug concentrations and minimize systemic toxicity. Studies have demonstrated that chemotherapy is often accompanied by cancer-associated immunogenic cell death (ICD) and that autophagy is involved in the induction of ICD. To improve the efficacy of local cancer chemotherapy, we hypothesized that the local delivery of chemotherapeutic plus autophagy-enhancing agents would enhance the promotive effects of ICD on the antitumor immune response. Here, we report that a low-dose chemotherapy/autophagy enhancing regimen (CAER) not only resulted in the increased death of B16F10 and 4T1 tumor cells, but also induced higher levels of autophagy in vitro. Importantly, the local delivery of the CARE drugs significantly inhibited tumor growth in B16F10 and 4T1 tumor-bearing mice. Systemic antitumor T-cell immunity was observed in vivo, including neoantigen-specific T-cell responses. Furthermore, bioinformatic analysis of human breast cancer and melanoma tissues showed that autophagy-associated gene expression was upregulated in tumor samples. Increased autophagy and immune cell infiltration in tumor tissues were positively correlated with good prognosis of tumor patients. This work highlights a new approach to improve the effects of local chemotherapy and enhance systemic antitumor immunity.

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“…Therefore, batch production will not be possible and it will never become a conventional drug ( 104 ). The advantage is that neo-antigen vaccines result in a potent T-cell response and induce a new population of specific T-cells in cancer patients that are able to kill cancer cells without damaging healthy tissues ( 104 , 108 , 109 ). Furthermore, pre-clinical trials are forthcoming with an aim to induce the T-cell response by ribonucleic acid (RNA)-based vaccine coding for multiple neo-epitopes ( 110 ).…”

Section: Peptide Vaccinementioning

confidence: 99%

Challenges and perspectives for immunotherapy in oesophageal cancer: A look to the future (Review)

et al. 2021

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Oesophageal cancer is one of the most aggressive malignancies with limited treatment options, thus resulting in a high morbidity and mortality. With 5-year survival rates of only 5-10%, oesophageal cancer holds a dismal prognosis for patients. In order to improve overall survival, the early diagnosis and tools for patient stratification for personalized treatment are urgent needs. A minority of oesophageal cancers belong to the spectrum of Lynch syndrome-associated cancers and are characterized by microsatellite instability (MSI). Microsatellite instability is a consequence of defective mismatch repair protein functions and it has been well characterized in other gastrointestinal tumours, such as colorectal and gastric cancer. In the latter, high levels of MSI are associated with a better prognosis and with an increased benefit to immune-based therapies. Therefore, similar therapeutic approaches could offer an opportunity of treatment for oesophageal cancer patients with MSI. Apart from immune checkpoint inhibitors, other immunotherapies such as adoptive T-cell transfer, peptide vaccine and oncolytic viruses are under investigation in oesophageal cancer patients. In the present review, the rationale and current knowledge about immunotherapies in oesophageal cancer are summarised.

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Progress in Neoantigen Targeted Cancer Immunotherapies

Cited by 31 publications

References 299 publications

MHC Phosphopeptides: Promising Targets for Immunotherapy of Cancer and Other Chronic Diseases

MHC Phosphopeptides: Promising Targets for Immunotherapy of Cancer and Other Chronic Diseases

A Local and Low-Dose Chemotherapy/Autophagy-Enhancing Regimen Treatment Markedly Inhibited the Growth of Established Solid Tumors Through a Systemic Antitumor Immune Response

Challenges and perspectives for immunotherapy in oesophageal cancer: A look to the future (Review)

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