Generation of Novel Tumour-Selective SEA Superantigen-Based Peptides with Improved Safety and Efficacy for Precision Cancer Immunotherapy

Journal article


Bashraheel, S. S., Al-Sulaiti, H. and Goda, S. K. 2024. Generation of Novel Tumour-Selective SEA Superantigen-Based Peptides with Improved Safety and Efficacy for Precision Cancer Immunotherapy. International Journal of Molecular Sciences. 25 (17), pp. 1-17. https://doi.org/10.3390/ijms25179423
AuthorsBashraheel, S. S., Al-Sulaiti, H. and Goda, S. K.
Abstract

Bacterial superantigens are T-cell-stimulatory protein molecules which produce massive cytokines and cause human diseases. Due to their ability to activate up to 20% of resting T-cells, they have effectively killed T-cell-dependent tumours in vivo. However, the intrinsic toxicity of whole SAg molecules highlights the urgent need to develop more effective and safer SAg-based immunotherapy. With its unique approach, our study is a significant step towards developing safer tumour-targeted superantigen peptides (TTSP). We identified the T-cell activation function regions on the SEA superantigen and produced variants with minimal lethality, ensuring a safer approach to cancer treatment. This involved the creation of twenty 50-amino-acid-long overlapping peptides covering the full-length SEA superantigen (P1-P20). We then screened these peptides for T-cell activation, successfully isolating two peptides (P5 and P15) with significant T-cell activation. These selected peptides were used to design and synthesise tumour-targeted superantigen peptides, which were linked to a cancer-specific third loop (L3) of transforming growth factor-α (TGF-α), TGFαL3 from either a C’ or N’ terminal with an eight-amino-acid flexible linker in between. We also produced several P15 variants by changing single amino acids or by amino acid deletions. The novel molecules were then investigated for cytokine production and tumour-targeted killing. The findings from our previous study and the current work open up new avenues for peptide-based immunotherapy, particularly when combined with other immunotherapy techniques, thereby ensuring effective and safer cancer treatment.

Keywordstumour-targeted superantigen; SEA superantigen; cancer combination therapy
Year2024
JournalInternational Journal of Molecular Sciences
Journal citation25 (17), pp. 1-17
PublisherMDPI
ISSN1422-0067
Digital Object Identifier (DOI)https://doi.org/10.3390/ijms25179423
Web address (URL)https://www.mdpi.com/1422-0067/25/17/9423
Publisher's version
License
File Access Level
Open
Output statusPublished
Publication dates
Online30 Aug 2024
Publication process dates
Deposited09 Sep 2024
Permalink -

https://repository.derby.ac.uk/item/q8974/generation-of-novel-tumour-selective-sea-superantigen-based-peptides-with-improved-safety-and-efficacy-for-precision-cancer-immunotherapy

Download files


Publisher's version
ijms-25-09423.pdf
License: CC BY 4.0
File access level: Open

  • 10
    total views
  • 3
    total downloads
  • 1
    views this month
  • 0
    downloads this month

Export as