Next-generation anti-OX40 antibodies for use in human lung cancer
Research type
Research Study
Full title
Developing next-generation anti-OX40 antibodies for use in human lung cancer
IRAS ID
356325
Contact name
Shobana Anpalakhan
Contact email
Sponsor organisation
University of Southampton
Duration of Study in the UK
3 years, 0 months, 0 days
Research summary
Antibody therapies have been promising cancer treatment options but many patients develop treatment resistance or intolerable side effects, emphasising the need for alternative treatments. One promising approach is using stimulatory antibodies targeting receptors, like OX40, on the surface of our immune system’s T-cells which could enhance T-cell action.
OX40 is highly expressed on lung cancer-associated T-cells and this has been associated with improved survival outcomes. However, clinical trials assessing OX40 antibodies have been underwhelming thus far, likely reflecting their insufficient efficacy thus more effective antibodies are required.
Antibody efficacy and mode of action can be determined by the structure of its stem, called the crystallisable fragment (Fc) domain, and the corresponding Fc receptors on tumour cells this Fc domain binds to. The antibody hinge region connects the Fc domain to the binding site, called the antigen binding fragment (Fab) domain, and can also affect antibody binding and efficacy. The Cragg group has generated novel hinge-modified OX40 antibodies and my preliminary work has demonstrated indications of potential increased efficacy with these hinge-modified antibodies.
Given the high OX40 expression in lung cancers and early studies using OX40 antibodies demonstrating good safety, exploration of these novel hinge-modified antibodies as a potential therapeutic option is warranted, particularly in patients with lung cancer.
This project aims to assess:
1. Whether hinge-modified OX40 antibodies drive improved antibody efficacy?
2. How they affect the activity of different T-cells and immune chemical secretion?
3. If the antibody Fc domain and tumour Fc receptor expression affect antibody efficacy?
4. Whether these OX40 antibodies drive improved efficacy in human lung cancer tissue
models?This work will evaluate novel hinge-modified OX40 antibodies for their ability to elicit T-cell activation and anti-tumour efficacy, using cell lines then human lung cancer tissue models, ultimately aiming to establish a new anti-cancer agent.
REC name
London - Dulwich Research Ethics Committee
REC reference
25/PR/0967
Date of REC Opinion
19 Aug 2025
REC opinion
Further Information Favourable Opinion