Biological effects of synthetic biomolecules that may either mimic or antagonise the function of hCG in the development of cancer and autoimmune disease

Human chorionic gonadotropin (hCG) is a hormone critical for successful pregnancy, partly by promoting maternal immune tolerance to fetal antigens. It achieves this by expanding immunoregulatory cells such as tolerogenic dendritic cells, regulatory T cells (Tregs), and regulatory B cells (Bregs). Interestingly, hCG is also secreted by certain tumours, helping them evade immune detection by creating a tolerogenic environment. This project aimed to design and synthesize small oligopeptide aptamers that specifically bind to the Beta and Alpha-helix regions of the hCG receptor, modulating its signalling. Peptide aptamers are a novel class of molecules with high binding specificity and can function as either agonists or antagonists. Naïve CD4+ T cells and B cells were isolated from PBMCs and cultured with these aptamers, both in the presence and absence of hCG. Flow cytometry was used to assess the expansion of Treg and Breg populations, and ELISA was employed to measure IL-10 secretion, a hallmark cytokine of immunoregulatory function. Two aptamers demonstrated distinct mechanisms of action. Aptamer A1 mimicked hCG signalling, promoting Treg and Breg differentiation and increased IL-10 secretion, indicating strong receptor binding and downstream activation. In contrast, Aptamer A2 inhibited these effects, acting as an antagonist by preventing receptor activation and suppressing regulatory cell expansion and IL-10 production. These findings highlight the therapeutic potential of hCG receptor-targeting aptamers. Agonistic aptamers like A1 could enhance immune tolerance, offering applications in treating autoimmune diseases. Conversely, antagonistic aptamers like A2 may block hCG-mediated immune suppression, providing a novel approach to treating hCG-secreting tumours by reactivating anti-tumour immunity.

Name dc:type.qualificationname

PhD

Level dc:type.qualificationlevel

PhD thesis

Grantor dc:publisher.institution

Middlesex University

Year dc:date.issued

2025

Author dc:creator

• Mousavinezhad Sarasia, E.

Identifier

oai:repository.mdx.ac.uk:367y0x

OAI identifier oai:identifier

oai:repository.mdx.ac.uk:367y0x