Patient-specific tumor-associated antigen repertoire

The patient-specific tumor-associated antigen repertoire refers to the unique collection of antigens, primarily neoantigens, expressed by an individual's tumor cells but not by healthy tissues [1]. These antigens arise from somatic mutations, such as single nucleotide variants or indels, which create novel protein sequences that the immune system can recognize as foreign [2]. In the context of personalized immunotherapy, this repertoire is identified through next-generation sequencing of a patient's tumor and healthy tissue, followed by bioinformatic prediction of which mutated peptides will most effectively bind to the patient's specific human leukocyte antigen (HLA) molecules [3]. Once identified, these antigens serve as the target for personalized cancer vaccines or adoptive T-cell therapies, designed to prime the patient's immune system to selectively destroy tumor cells [4]. This approach aims to overcome the limitations of targeting shared tumor antigens, which often suffer from central tolerance or off-target toxicity in normal tissues [5]. By focusing on the unique mutational landscape of a single patient, these therapies provide a highly specific mechanism of action that minimizes damage to healthy cells while potentially providing long-lasting immunological memory against recurrence [6]. [1] Sahin U, Türeci Ö. Science. 2018. [2] Ott PA, et al. Nature. 2017. [3] Blass E, Ott PA. Nat Rev Clin Oncol. 2021. [4] Hu Z, et al. Nat Med. 2021. [5] Schumacher TN, Schreiber RD. Science. 2015. [6] Keskin DB, et al. Nature. 2019.

Other names

Personalized neoantigen repertoirePatient-specific neoantigensIndividualized tumor-associated antigensTumor neoantigen landscapePersonalized tumor-associated antigen repertoire

Induction of a de novo, patient-specific T-cell response against unique tumor neoantigens presented on HLA molecules.