Tumour infiltrating lymphocyte (TIL) therapy, in which autologous T cells from tumour biopsies are expanded ex vivo before reinfusion, has proven successful in individuals with metastatic melanoma and is being trialled for other cancers. However, the effectiveness of TILs is often limited by their exhaustion resulting from intratumoral antigen exposure and prolonged ex vivo expansion. Cells can be engineered to maximize effector functions but this might enhance the toxicity of non-antigen-specific T cells within the expanded TIL population and would complicate the production of TIL therapies.

Using gene-delivery vectors to target and functionally enhance tumour-specific T cells in vivo is an alternative immunotherapeutic approach. Peptide–MHC (pMHC)-displaying lipid nanoparticles have been shown to deliver mRNA cargo to antigen-specific T cells in vivo; similarly, pMHC-pseudotyped lentiviral gene delivery has been tested in vitro, and could enable prolonged transgene expression to sustain antitumour responses. In this preprint (not peer-reviewed), Xu et al. show that pMHC-pseudotyped retroviruses can deliver therapeutic cargo to tumour-specific T cells in vivo and improve tumour control.