Evaluation of alpha v beta 6 integrin in cancer and non-cancer tissue.

• Research type

  Research Study

• Full title

  Evaluation of alpha v beta 6 integrin in cancer and non-cancer tissue as a potential for targeted cancer therapy

• IRAS ID

  323119

• Contact name

  Adam Frampton

• Contact email

  adam.frampton@surrey.ac.uk

• Sponsor organisation

  University of Surrey

• Duration of Study in the UK

  3 years, 0 months, 1 days

• Research summary

  Integrins are a large family of heterodimeric transmembrane receptors that mediate cell-substratum adhesion. αvβ6 is an epithelial-specific integrin that is a receptor for the extracellular matrix (ECM) proteins fibronectin, vitronectin, tenascin and the latency associated peptide (LAP) of TGF-β. Integrin αvβ6 is not expressed in healthy adult epithelia but is upregulated during wound healing and in cancer. αvβ6 has been shown to modulate invasion, inhibit apoptosis, regulate the expression of matrix metalloproteases (MMPs) and activate TGF-β1. There is increasing evidence, primarily from in vitro studies, that suggest that αvβ6 may actually promote carcinoma progression.
  Avb6 is a potential therapeutic target for a new oncolytic virus (Trocept) and various antibody and antibody-drug conjugates as well as means to stage cancer using PET imaging specific for avb6 expression

  Although there is established data in the literature describing avb6 expression in various cancers, these have been small numbers and often very small subsets and almost exclusively primary tumours. More recently tissue microarray studies have confirmed 80-100% prevalence of expression in many solid cancers, but again they are small sample areas of the whole tumour.
  In order to underpin and give robust justification for taking a new targeted therapy in the clinic it is important to evaluate the map out the expression of avb6 in patients cancers that are experienced in routine practice. In particular we propose to examine the level of expression, the selectivity and location of the expression (is it on the invasive margin or more homogenous in the tumour?) and also to examine the immune microenvironment in tumours with respect to avb6 staining.

  Summary of results
  Most cancers that form solid tumours are known as carcinomas, and they are responsible for the majority of cancer-related deaths. Developing new treatments that can specifically target cancer cells while avoiding healthy tissues is an important area of research.
  In this study, researchers investigated a protein called αvβ6 integrin, which is found on the surface of some cancer cells. Tissue samples from fifteen common types of carcinoma, including samples from cancers that had spread to other parts of the body, were examined using a laboratory staining technique. The results showed that αvβ6 integrin was present in over 90% of several common epithelial cancer types. Importantly, the protein remained present, or was found at even higher levels, in cancers that had spread. In contrast, it was absent or only weakly present in most healthy adult tissues, apart from parts of the bladder and stomach.
  The study also tested a new experimental cancer-targeting delivery system called TROCEPT, which is designed to recognise cells carrying αvβ6 integrin and deliver potential treatments directly into those cells. Fresh tumour samples from different cancer types were collected and tested in the laboratory. Pancreatic cancer samples showed particularly promising results. In all five pancreatic cancer samples that contained αvβ6 integrin, TROCEPT successfully entered the cancer cells but did not infect the surrounding healthy tissue.
  Overall, the findings support αvβ6 integrin as a promising target for future cancer therapies. Because this protein is found on many different cancers, remains present after cancer has spread, and is largely absent from healthy tissues, it may help future treatments target cancer cells more accurately while reducing effects on normal tissues. These findings provide important information to support the continued development and testing of targeted cancer therapies.

• REC name

  London - Bromley Research Ethics Committee

• REC reference

  23/PR/0221

• Date of REC Opinion

  27 Mar 2023

• REC opinion

  Further Information Favourable Opinion