Malekzadeh et al. developed a high-throughput screening method involving mutation-containing tandem minigenes, TILs, and autologous APCs to identify T cells recognizing mutations in the 8 most commonly mutated TP53 positions. In 28 patients with PBL and TIL samples, 11 were found to have CD4+ and/or CD8+ TILs reactive against TP53 neoantigens in an HLA-restricted manner. Some T cells recognized endogenously-presented mutated p53 neoepitopes and showed upregulation of degranulation and cytolysis markers. The researchers generated a library of 9 p53 neoantigen-specific TCRs, indicating potential for off-the-shelf targeted immunotherapy.
Neoantigen screening identifies broad TP53 mutant immunogenicity in patients with epithelial cancers
Spotlight(1) Malekzadeh P (2) Pasetto A (3) Robbins PF (4) Parkhurst MR (5) Paria BC (6) Jia L (7) Gartner JJ (8) Hill V (9) Yu Z (10) Restifo NP (11) Sachs A (12) Tran E (13) Lo W (14) Somerville RP (15) Rosenberg SA (16) Deniger DC
Malekzadeh et al. developed a high-throughput screening method involving mutation-containing tandem minigenes, TILs, and autologous APCs to identify T cells recognizing mutations in the 8 most commonly mutated TP53 positions. In 28 patients with PBL and TIL samples, 11 were found to have CD4+ and/or CD8+ TILs reactive against TP53 neoantigens in an HLA-restricted manner. Some T cells recognized endogenously-presented mutated p53 neoepitopes and showed upregulation of degranulation and cytolysis markers. The researchers generated a library of 9 p53 neoantigen-specific TCRs, indicating potential for off-the-shelf targeted immunotherapy.