Patient-specific tumor neoantigen peptide–HLA class I complex (Neoantigen-HLA complex)

The patient-specific tumor neoantigen peptide–HLA class I complex is a highly specific molecular target located on the surface of malignant cells. It is composed of a neoantigen—a peptide fragment derived from a tumor-specific somatic mutation—presented by the patient's own Human Leukocyte Antigen (HLA) class I molecules [4, 11]. Because these neoantigens are not expressed in healthy tissues, they serve as ideal targets for precision immunotherapy, minimizing the risk of off-target toxicity [7, 17]. The complex is recognized by T-cell receptors (TCRs), which initiate a cascade of immune signaling leading to the destruction of the tumor cell by cytotoxic T-lymphocytes [11, 16]. In personalized adoptive cell therapies like NeoTCR-P1, a patient's T cells are engineered to express a TCR that specifically binds to these unique neoantigen-HLA complexes [1, 4]. This approach is designed to treat various solid tumors by leveraging the individual's unique mutation blueprint to direct an effective immune response [6, 8]. Therapeutic success depends on the stable presentation of the neoantigen and the persistence of the engineered T cells within the tumor microenvironment [5, 12]. Challenges to this strategy include immune escape mechanisms such as the loss of HLA heterozygosity or downregulation of the antigen presentation machinery [5, 13].

Other names

Tumor-specific neoantigen-MHC class I complexPatient-specific neoepitope-HLA complexNeoantigen-HLA-I complexpHLA complexNeoantigen-targeted HLA complex

The target complex is recognized by engineered T-cell receptors (TCRs) on the surface of autologous adoptive T-cells (NeoTCR-P1). Binding of the TCR to the specific neoantigen-HLA complex triggers T-cell activation, leading to the release of perforins and granzymes that induce cytotoxic killing of the tumor cell [1, 11].