Mapping the Immune System's Peptide Targets in HPV16-Caused Cancers for T Cell Therapy

Tumor-infiltrating lymphocytes from 12 HPV16-induced tumors were screened using HLA-peptide multimers and a functional platform using single HLA class I allele-engineered antigen presenting cells. This approach identified CD8+ T cell epitopes without prior assumptions about which peptides would be presented. Reactive T cell receptors were isolated and tested for tumor cell killing activity.

HPV16-caused cancers affect hundreds of thousands of people annually worldwide. While preventive vaccines exist, treatments for established HPV cancers are needed. Knowing exactly which viral peptides the immune system targets allows development of therapeutic vaccines and engineered T cell therapies. The identified tumor-reactive TCRs could be manufactured into off-the-shelf T cell therapies for patients whose immune systems aren't fighting the cancer effectively on their own.

Peptide-based cancer immunotherapy is advancing rapidly, with HPV cancers being ideal targets because the viral proteins are truly foreign to the body. This study provides the epitope map needed for both therapeutic peptide vaccines and TCR-engineered T cell transfer — two of the most promising approaches in cancer immunotherapy. As personalized cell therapies become more accessible, having a library of validated tumor-reactive TCRs for common cancers will be invaluable.

The study included only 12 tumors, limiting the completeness of the epitope map. HLA diversity means some rare HLA alleles may not have been represented. TCR reactivity was confirmed for most but not all isolated receptors. The study was performed in vitro — clinical efficacy of these TCRs in adoptive cell therapy has not been demonstrated. Tumor heterogeneity and immune evasion mechanisms could limit therapeutic effectiveness in vivo.