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Design, synthesis, and initial immunological evaluation of glycoconjugates based on saponin adjuvants and the Tn antigen.

ABSTRACT: We report the first synthesis and immunological evaluation of a new glycoconjugate design based on streamlined saponin adjuvants and the Tn carbohydrate antigen. While the novel synthetic constructs induced moderate antibody responses in mice, the versatile chemical platform is amenable to further structure-activity optimizations for the development of self-adjuvanting glycoconjugate cancer vaccines.

SUBMITTER: Fuentes R

PROVIDER: S-EPMC8552335 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Design, synthesis, and initial immunological evaluation of glycoconjugates based on saponin adjuvants and the Tn antigen.

Fuentes Roberto R Aguinagalde Leire L Sacristán Nagore N Fernández-Tejada Alberto A

Chemical communications (Cambridge, England) 20211028 86

We report the first synthesis and immunological evaluation of a new glycoconjugate design based on streamlined saponin adjuvants and the Tn carbohydrate antigen. While the novel synthetic constructs induced moderate antibody responses in mice, the versatile chemical platform is amenable to further structure-activity optimizations for the development of self-adjuvanting glycoconjugate cancer vaccines. ...[more]

PMID: 34647563

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Project description:BackgroundWe have previously shown that HCC patients and healthy subjects are equally responsive to a RNAdjuvant®, a novel TLR-7/8/RIG-I agonist based on noncoding RNA developed by CureVac, by an ex vivo evaluation. However, the immunological effect of adjuvants on immune cells from cancer patients undergoing chemotherapy remains to be demonstrated. Different adjuvants currently used in cancer vaccine clinical trials were evaluated in the present study on immune cells from cancer patients before and after chemotherapy in an ex vivo setting.MethodsPBMCs were obtained from 4 healthy volunteers and 23 patients affected by either colon (OMA) or lung cancer (OT). The effect of CpG, Poly I:C, Imiquimod and RNA-based adjuvant (RNAdjuvant®) was assessed using a multiparametric approach to analyze network dynamics of early immune responses. Evaluation of CD80, CD86 and HLA-DR expression as well as the downstream effect on CD4+ T cell phenotyping was performed by flow cytometry; cytokine and chemokine production was evaluated by Bio-Plex ProTM.ResultsTreatment with RNAdjuvant® induced the strongest response in cancer patients in terms of activation of innate and adoptive immunity. Indeed, CD80, CD86 and HLA-DR expression was found upregulated in circulating dendritic cells, which promoted a CD4+ T cell differentiation towards an effector phenotype. RNAdjuvant® was the only one to induce most of the cytokines/chemokines tested with a pronounced Th1 cytokine pattern. According to the different parameters evaluated in the study, no clear cut difference in immune response to adjuvants was observed between healthy subjects and cancer patients. Moreover, in the latter group, the chemotherapy treatment did not consistently correlate to a significant altered response in the different parameters.ConclusionsThe present study is the first analysis of immunological effects induced by adjuvants in cancer patients who undergo chemotherapy, who are enrolled in the currently ongoing cancer vaccine clinical trials. The results show that the RNAdjuvant® is a potent and Th1 driving adjuvant, compared to those tested in the present study. Most importantly, it is demonstrated that chemotherapy does not significantly impair the immune system, implying that cancer patients are likely to respond to a cancer vaccine even after a chemotherapy treatment.

Dataset Information

Design, synthesis, and initial immunological evaluation of glycoconjugates based on saponin adjuvants and the Tn antigen.

Publications

Design, synthesis, and initial immunological evaluation of glycoconjugates based on saponin adjuvants and the Tn antigen.

Similar Datasets

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