Synthesis and immunological evaluation of N-acyl modified Globo H derivatives as anticancer vaccine candidates

2021 ◽  
Author(s):  
Canjia Zhai ◽  
Xiu-Jing Zheng ◽  
Cheng-Cheng Song ◽  
Xin-Shan Ye
Keyword(s):  
T Cell ◽  
Carbohydrate Antigen ◽  
Vaccine Candidates ◽  
Antitumor Vaccine ◽  
Cancer Immunotherapies ◽  
Anticancer Vaccine ◽  
Immunological Evaluation

Globo H is a tumor-associated carbohydrate antigen (TACA), which serves as a valuable target for antitumor vaccine or cancer immunotherapies. However, most TACAs are T-cell-independent and they cannot induce powerful...

Synthesis and immunological evaluation of N-acyl modified Tn analogues as anticancer vaccine candidates

2016 ◽  
Vol 24 (4) ◽  
pp. 915-920 ◽  
Author(s):  
Chengcheng Song ◽  
Shuang Sun ◽  
Chang-Xin Huo ◽  
Qin Li ◽  
Xiu-Jing Zheng ◽  
...  
Keyword(s):  
Vaccine Candidates ◽  
Anticancer Vaccine ◽  
Immunological Evaluation

Syntheses and Immunological Evaluation of Self‐Adjuvanting Clustered N ‐Acetyl and N ‐Propionyl Sialyl‐Tn Combined with a T‐helper Cell Epitope as Antitumor Vaccine Candidates

2018 ◽  
Vol 130 (27) ◽  
pp. 8351-8356 ◽  
Author(s):  
Tsung‐Che Chang ◽  
Yoshiyuki Manabe ◽  
Yukari Fujimoto ◽  
Shino Ohshima ◽  
Yoshie Kametani ◽  
...  
Keyword(s):  
Cell Epitope ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Vaccine Candidates ◽  
Antitumor Vaccine ◽  
Immunological Evaluation ◽  
Sialyl Tn

Prediction of Prophylactic Peptide Vaccine Candidates for Human Papillomavirus (HPV): An Immunoinformatics and Reverse Vaccinology Approach

2020 ◽  
Vol 17 ◽  
Author(s):  
Mehreen Ismail ◽  
Zureesha Sajid ◽  
Amjad Ali ◽  
Xiaogang Wu ◽  
Syed Aun Muhammad ◽  
...  
Keyword(s):  
T Cells ◽  
Human Papillomavirus ◽  
T Cell ◽  
Binding Affinity ◽  
Cd8 T Cells ◽  
Reverse Vaccinology ◽  
Host Immune System ◽  
T Cell Epitopes ◽  
Multiple Alleles ◽  
Vaccine Candidates

Background: Human Papillomavirus (HPV) is responsible for substantial morbidity and mortality worldwide. We predicted immunogenic promiscuous monovalent and polyvalent T-cell epitopes from the polyprotein of the Human Papillomavirus (HPV) using a range of bioinformatics tools and servers. Methods: We used immunoinformatics and reverse vaccinology-based approaches to design prophylactic peptides by antigenicity analysis, Tcell epitopes prediction, proteasomal and conservancy evaluation, host-pathogen protein interactions, and in silico binding affinity analysis. Results: We found two early proteins (E2 and E6) and two late proteins (L1 and L2) of HPV as potential vaccine candidates. Of these proteins (E2, E6, L1 & L2), 2-epitopes of each candidate protein for multiple alleles of MHC class I and II bearing significant binding affinity (>-6.0 kcal/mole). These potential epitopes for CD4+ and CD8+ T-cells were also linked to design polyvalent construct using GPGPG linkers. Cholera toxin B and mycobacterial heparin-binding hemagglutinin adjuvant with a molecular weight of 12.5 and 18.5 kDa were used for epitopes of CD4+ and CD8+ T-cells respectively. The molecular docking indicated the optimum binding affinity of HPV peptides with MHC molecules. This interaction showed that our predicted vaccine candidates are suitable to trigger the host immune system to prevent HPV infections. Conclusion: The predicted conserved T-cell epitopes would contribute to the imminent design of HPV vaccine candidates, which will be able to induce a broad range of immune-responses in a heterogeneous HLA population.

scholarly journals Synthesis and immunological evaluation of synthetic peptide based anti-SARS-CoV-2 vaccine candidates

2021 ◽  
Author(s):  
Qingyu Zhao ◽  
Yanan Gao ◽  
Min Xiao ◽  
Xuefei Huang ◽  
Xuanjun Wu
Keyword(s):  
Synthetic Peptide ◽  
Spike Protein ◽  
Effective Vaccine ◽  
The Novel ◽  
Vaccine Candidates ◽  
Peptide Epitopes ◽  
Novel Coronavirus ◽  
Immunological Evaluation

For prevention of the coronavirus disease 2019 caused by the novel coronavirus SARS-CoV-2, an effective vaccine is critical. Herein, several potential peptide epitopes from the spike protein of SARS-CoV-2 have...

scholarly journals Single-cell RNA sequencing reveals distinct cellular factors for response to immunotherapy targeting CD73 and PD-1 in colorectal cancer

2021 ◽  
Vol 9 (7) ◽  
pp. e002503
Author(s):  
Miok Kim ◽  
Yong Ki Min ◽  
Jinho Jang ◽  
Hyejin Park ◽  
Semin Lee ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trials ◽  
T Cells ◽  
T Cell ◽  
In Vivo Models ◽  
Single Cell Rna Sequencing ◽  
Tcr Diversity ◽  
Cancer Immunotherapies

BackgroundAlthough cancer immunotherapy is one of the most effective advanced-stage cancer therapies, no clinically approved cancer immunotherapies currently exist for colorectal cancer (CRC). Recently, programmed cell death protein 1 (PD-1) blockade has exhibited clinical benefits according to ongoing clinical trials. However, ongoing clinical trials for cancer immunotherapies are focused on PD-1 signaling inhibitors such as pembrolizumab, nivolumab, and atezolizumab. In this study, we focused on revealing the distinct response mechanism for the potent CD73 ectoenzyme selective inhibitor AB680 as a promising drug candidate that functions by blocking tumorigenic ATP/adenosine signaling in comparison to current therapeutics that block PD-1 to assess the value of this drug as a novel immunotherapy for CRC.MethodsTo understand the distinct mechanism of AB680 in comparison to that of a neutralizing antibody against murine PD-1 used as a PD-1 blocker, we performed single-cell RNA sequencing of CD45+ tumor-infiltrating lymphocytes from untreated controls (n=3) and from AB680-treated (n=3) and PD-1-blockade-treated murine CRC in vivo models. We also used flow cytometry, Azoxymethane (AOM)/Dextran Sulfate Sodium (DSS) models, and in vitro functional assays to validate our new findings.ResultsWe initially observed that the expressions of Nt5e (a gene for CD73) and Entpd1 (a gene for CD39) affect T cell receptor (TCR) diversity and transcriptional profiles of T cells, thus suggesting their critical roles in T cell exhaustion within tumor. Importantly, PD-1 blockade significantly increased the TCR diversity of Entpd1-negative T cells and Pdcd1-positive T cells. Additionally, we determined that AB680 improved the anticancer functions of immunosuppressed cells such as Treg and exhausted T cells, while the PD-1 blocker quantitatively reduced Malat1high Treg and M2 macrophages. We also verified that PD-1 blockade induced Treg depletion in AOM/DSS CRC in vivo models, and we confirmed that AB680 treatment caused increased activation of CD8+ T cells using an in vitro T cell assay.ConclusionsThe intratumoral immunomodulation of CD73 inhibition is distinct from PD-1 inhibition and exhibits potential as a novel anticancer immunotherapy for CRC, possibly through a synergistic effect when combined with PD-1 blocker treatments. This study may contribute to the ongoing development of anticancer immunotherapies targeting refractory CRC.

scholarly journals Manipulation of Glucose Availability to Boost Cancer Immunotherapies

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2940
Author(s):  
Federica Marchesi ◽  
Debora Vignali ◽  
Beatrice Manini ◽  
Alessandra Rigamonti ◽  
Paolo Monti
Keyword(s):  
T Cell ◽  
Metabolic Regulation ◽  
Cell Function ◽  
Immune Cell ◽  
Deep Level ◽  
T Cell Responses ◽  
Cell Responses ◽  
T Cell Function ◽  
Cancer Tissues ◽  
Cancer Immunotherapies

The orchestration of T cell responses is intimately linked to the execution of metabolic processes, both in homeostasis and disease. In cancer tissues, metabolic alterations that characterize malignant transformation profoundly affect the composition of the immune microenvironment and the accomplishment of an effective anti-tumor response. The growing understanding of the metabolic regulation of immune cell function has shed light on the possibility to manipulate metabolic pathways as a strategy to improve T cell function in cancer. Among others, glucose metabolism through the glycolytic pathway is central in shaping T cell responses and emerges as an ideal target to improve cancer immunotherapy. However, metabolic manipulation requires a deep level of control over side-effects and development of biomarkers of response. Here, we summarize the metabolic control of T cell function and focus on the implications of metabolic manipulation for the design of immunotherapeutic strategies. Integrating our understanding of T cell function and metabolism will hopefully foster the forthcoming development of more effective immunotherapeutic strategies.

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