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ImmuniT Platform for Improved Neoantigen Prediction in Lung Cancer.
Stephanie J Hachey1, Alexander G Forsythe2, Hari B Keshava3
1Molecular Biology and Biochemistry, University of California, Irvine, Irvine, 92697, CA, USA.
Biorxiv : the Preprint Server for Biology
|April 1, 2025
Summary
The ImmuniT platform enhances neoantigen identification for lung cancer immunotherapy, improving T cell activation. This novel approach detects more immunogenic targets, offering better personalized treatment options for patients resistant to current therapies.
Area of Science:
- Oncology
- Immunology
- Bioinformatics
Background:
- Lung cancer is a leading cause of cancer death, often presenting as advanced and treatment-resistant disease.
- Current immunotherapies are limited by inadequate tumor recognition and patient-specific immune responses.
- Existing neoantigen discovery methods may miss immunogenic targets, especially those with low or heterogeneous expression.
Purpose of the Study:
- To develop and evaluate the ImmuniT platform for enhanced neoantigen identification in non-small cell lung cancer (NSCLC).
- To improve the accuracy and breadth of neoantigen prediction for more precise personalized immunotherapy.
Main Methods:
- Recruitment of NSCLC patients and collection of tumor and blood samples under IRB approval.
- Processing of tumor samples to enhance neoantigen expression and co-culture with lymphocytes to expand neoantigen-reactive T cells.
- Utilizing the nextneopi pipeline integrating TMB, HLA typing, and transcriptomic data, with MHC:epitope complex validation via tetramer staining.
Main Results:
- The ImmuniT platform demonstrated superior neoantigen prediction and T cell activation in vitro compared to conventional methods.
- Identified two neoantigens missed by standard approaches in one patient, which stimulated both tumor-infiltrating and peripheral blood lymphocytes.
- Detected a broader spectrum of immunogenic targets across all tested NSCLC samples.
Conclusions:
- The ImmuniT platform significantly improves neoantigen detection in NSCLC, identifying a wider range of tumor-specific antigens.
- Enhanced neoantigen discovery by ImmuniT has the potential to improve T cell activation and optimize immunotherapy efficacy.
- This platform represents a promising advancement for personalized treatment strategies in lung cancer, particularly for immunotherapy-resistant patients.
