6533b7d1fe1ef96bd125d69f

RESEARCH PRODUCT

Anti-p53-directed immunotherapy of malignant disease

Matthias TheobaldRienk Offringa

subject

MutationT-Lymphocytesmedicine.medical_treatmentT-cell receptorGenetic TherapyImmunotherapyBiologymedicine.disease_causeMajor histocompatibility complexCell therapyGenes T-Cell ReceptorCancer immunotherapyAntigenNeoplasmsmedicineCancer researchbiology.proteinHumansMolecular MedicineImmunotherapyTumor Suppressor Protein p53ReceptorMolecular Biology

description

Mutation and aberrant expression of the p53 tumour suppressor protein are the most frequent molecular alterations in human malignancy. Peptides derived from the p53 protein and presented by major histocompatibility complex molecules for T-cell recognition could serve as universal tumour-associated antigens for cancer immunotherapy. Because p53 normally functions as a ubiquitously expressed self-protein, controlling cell-cycle progression and apoptosis, it also represents a paradigm target molecule for tumour-reactive yet self-antigen-specific T cells. Tailoring p53-based cancer immunotherapy thus requires both interference with p53-specific self-tolerance and induction of the entire repertoire of p53-reactive T cells. Transferring selected T-cell receptor genes into human T cells offers a novel and appealing strategy to meet these requirements.

https://doi.org/10.1017/s1462399403006173