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Design and evaluation of a multiepitope vaccine for pancreatic cancer using immune-dominant epitopes derived from the signature proteome in expression datasets

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Abstract

Pancreatic cancer is a highly aggressive and often lethal malignancy with limited treatment options. Its late-stage diagnosis and resistance to conventional therapies make it a significant challenge in oncology. Immunotherapy, particularly cancer vaccines, has emerged as a promising avenue for treating pancreatic cancer. Multi-epitope vaccines, designed to target multiple epitopes derived from various antigens associated with pancreatic cancer, have gained attention as potential candidates for improving therapeutic outcomes. In this study, we have explored transcriptomics and protein expression databases to identify potential upregulated proteins in pancreatic cancer cells. After examining a total of 21,054 proteins from various databases, it was discovered that 143 proteins expressed differently in malignant and healthy cells. The CTL, HTL and BCE epitopes were predicted for the shortlisted proteins. 51,840 vaccine constructs were created by concatenating CTL, HTL, and B-cell epitopes in the respective sequences. The best 86 structures were selected from a set of 51,840 designs after they were analyzed for vaxijenicity, allergenicity, toxicity, and antigenicity scores. In further simulation of the immune response using constructs, it was found that 41417, 37961, and 40841 constructs could produce a strong immune response when injected. Further, it was found that construct 37961 showed stronger interaction and stability with TLR-9 as determined from the large-scale molecular dynamics simulations. Moreover, the 37961 construct has shown interactions with TLR-9 suggests its potential in inducing immune response. In addition, construct 37961 has shown 100% predicted solubility in the E. coli expression system. Overall, the study indicates the designed construct 37961 has the potential to induce an anti-tumor immune response and long-standing protection pending further studies.

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Funding

SB acknowledges the National Institute of Technology Warangal for funding in the form of postdoctoral fellowship.

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  1. Department of Biotechnology, National Institute of Technology-Warangal, Warangal, Telangana, 506004, India

    Sooram Banesh, Nupoor Patil, Vihadhar Reddy Chethireddy, Arnav Bhukmaria & Prakash Saudagar

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12032_2024_2334_MOESM5_ESM.jpg

Figure S1. Top vaccine constructs modelled structures with their corresponding Ramachandran plots. (A) 41417, (B) 40841, (C) 37385, (D) 37962, (E) 37937, (F) 37997, (G) 37386, (H) 51785 and (I) 37097. All of the constructs contains large random coil content and most residues are in disallowed regions. Supplementary file5 (JPG 6262 KB)

12032_2024_2334_MOESM6_ESM.jpg

Figure S2. Vaccine constructs solubility assessment for (A) 41417, (B) 40841, and (C) 37385 constructs determined from CCSol server. All of the constructs are highly soluble in E. coli system. Supplementary file6 (JPG 1453 KB)

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Banesh, S., Patil, N., Chethireddy, V.R. et al. Design and evaluation of a multiepitope vaccine for pancreatic cancer using immune-dominant epitopes derived from the signature proteome in expression datasets. Med Oncol 41, 90 (2024). https://doi.org/10.1007/s12032-024-02334-4

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