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Intratumoural activation of CAR T cells via focused ultrasound
This issue highlights the engineering of T cells to infiltrate pancreatic tumours, a bispecfic antibody for the rejuvenation of tumour-specific T cells, checkpoint-blockade antibodies conjugated to glucosylated polymers for glioblastoma therapy, the site-specific PEGylation of IL-2, an antibody for the concurrent depletion of tumour cells and immunosuppressive cells, an organoid-based screen for epigenetic inhibitors that stimulate antigen presentation, the control of the activity of CAR T cells via local elevations in temperature, the direct reprogramming of natural killer cells, an orally administered gel generating systemic antitumour immunity, and nanobody–antigen adducts for the induction of antigen-specific tolerance.
The cover illustrates that T cells can be engineered to express a chimaeric antigen receptor within tumours when heat is locally generated by pulses of focused ultrasound.
The efficacy of adoptive cell therapy for pancreatic cancer can be augmented by antigen-specific cytotoxic T cells genetically engineered to overexpress a C-X-C chemokine receptor whose ligand is highly expressed by pancreatic cancer cells.
Forced expression of C-X-C chemokine receptor type 6 in antigen-specific T cells enhanced the recognition and lysis of pancreatic cancer cells and the efficacy of adoptive cell therapy for pancreatic cancer.
A bispecific antibody targeting the T-cell co-receptor CD3ε and the immune checkpoint programmed-death ligand 1 on dendritic cells rejuvenates tumour-specific CD8 T cells, leading to durable antitumour responses in murine models of cancer.
Monoclonal antibodies conjugated with multiple polymer chains functionalized to target glucose transporter 1 and detaching in the reductive tumour microenvironment augment the potency and safety of checkpoint blockade therapy for glioblastoma.
Orthogonally conjugating the cytokine interleukin-2 to poly(ethylene glycol) moieties at defined protein sites improves its pharmacokinetics and half-life as well as its therapeutic performance in mouse models of autoimmune diseases.
The concurrent depletion of tumour cells and immunosuppressive cells via a monoclonal antibody targeting a common surface marker prevents tumours from acquiring resistance to therapies involving immune checkpoint blockade.
Epigenetic inhibitors that promote antigen presentation and potentiate T-cell-mediated cytotoxicity can be identified by a high-throughput screen of cytotoxic T-cell activity in breast tumour organoids.
The activity of engineered T cells within tumours can be controlled via the heat generated by pulses of focused ultrasound by modifying the cells to express a chimeric antigen receptor under the control of a promoter for the heat-shock protein.
Spatial control of the production of immunomodulatory biologics by CAR T cells engineered with synthetic gene switches that respond to mild elevations in temperature enhances the cells’ antitumour activity.
Human natural killer cells with potent anticancer activity can be directly reprogrammed from somatic cells using pluripotency transcription factors and an optimized reprogramming medium.
An orally administered gel that is retained in the colon modulates the gut microbiome of mice with murine tumours, inducing systemic memory-T-cell responses and amplifying the antitumour activity of a checkpoint inhibitor.
Nanobodies recognizing class-II major-histocompatibility-complex molecules and conjugated to relevant self-antigens confer protection against autoimmune diseases in mice.