Cancer immunotherapy articles from across Nature Portfolio

Early clinical data on in vivo CAR-T cell therapy for multiple myeloma reveals key mechanistic insights and could mark the beginning of a new era of fast, streamlined and accessible immunotherapies.

We developed a nanoadjuvant platform that targets early endosome membranes in tumour cells, triggering their pyroptosis and the release of pyroptosomes, which act as an in situ vaccine against the tumour. In preclinical cancer models featuring multiple metastases, this nanoplatform enabled spatiotemporal induction of robust immune responses, resulting in systemic tumour eradication and long-lasting antitumour immunity.

Tumour location dictates ferroptosis resistance. A study indicates that peritumoural adipose tissue aids tumours in evading ferroptosis by supplying tryptophan metabolites, including kynurenine and 3-hydroxykynurenine, which block NCOA4-mediated ferritinophagy to lower levels of labile iron and suppress lipid peroxidation.

Reduced expression of STING in cancer cells due to ER and Golgi dysfunction enables tumor immune escape and limits STING targeted therapies. The authors here develop a cell membrane derived nanodisc system ND-cGAMP-HP that delivers activated STING directly to tumor cells bypassing ER Golgi translocation which activates the IFN-I signaling pathway and induces potent cellular immune responses.

Standard of care CD19-targeting CAR-T therapy for Relapsed-Refractory Diffuse Large B Cell Lymphoma (r/r DLBCL) faces frequent resistance often driven by regulatory T cell (Treg) activation. This study identifies Timosaponin AIII (TAIII) as A2AR inhibitor for enhanced CAR-T activity while depleting CAR-Treg formation.

In this Journal Club, Terrazas and Peón discuss a study that identifies a recurrent CTNNB1 mutation that generates shared neoantigens amenable to engineered T cell receptor (TCR)-T cell recognition. The work demonstrates potent antitumour activity across models and highlights the potential of targeting public mutations to broaden TCR-T cell immunotherapy for solid tumours.

Early clinical data on in vivo CAR-T cell therapy for multiple myeloma reveals key mechanistic insights and could mark the beginning of a new era of fast, streamlined and accessible immunotherapies.