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Chimeric antigen receptor (CAR) T cell therapies have revolutionized the treatment of haematological malignancies; however, their application in solid tumors remains challenging. CAR technology has now extended beyond T-cells and applied to other immune cells, including NK cells and macrophages. Alternative immune-engineering approaches, including direct in vivo immune cell engineering, are also emerging. A tumor infiltrating lymphocyte (TIL)-based therapy has recently received FDA approval as the first cellular therapy for solid tumors.
With this Collection, a partnership between Nature Communications, Communications Medicine, Communications Biology, and Scientific Reports, we welcome submissions of primary research papers that focus on immune cell engineering for cancer therapy. The journals are particularly interested in preclinical studies proposing new engineering strategies and therapeutic developments.
Nature Communications, Communications Medicine, and Scientific Reports are also interested in publishing high-quality clinical research in the field.
We will highlight relevant papers in this Collection; unfortunately, we cannot guarantee that any individual paper will be included in the Collection.
CAR-T cell therapy has been shown to be effective in immunotherapy for treatment of several different tumours. Here the authors show pre-specified interim outcomes from a P-BCMA-ALLO1 trial with BCMA targeted CAR-T therapy in multiple myeloma.
89ZED88082A is a zirconium-89-labeled one-armed anti-CD8α antibody for the non-invasive whole-body visualization of CD8 + T-cells by positron emission tomography (PET). Here the authors report the results of a phase 2 study of 89ZED88082A for whole-body CD8 + T-cell PET imaging in patients with large B-cell lymphoma before and during CD19-directed CAR T-cell therapy.
Off-the-shelf, on-demand allogeneic CAR-T cells could represent a therapeutic alternative to autologous products for cancer therapy. Here the authors report the preclinical characterization of off-the-shelf CRISPR-Cas9– edited IL-13Rα2-specific allogeneic universal CAR-T cells and the results of a first-in-human phase I trial in patients with high-grade glioma.
A first-in-human clinical trial of iPS cell-derived invariant natural killer T cells in patients with recurrent head and neck cancer demonstrated safety and early signs of efficacy, showing tumor growth suppression and activation of immune pathways.
CAR T cell therapies have been developed to treat paediatric diffuse intrinsic pontine glioma (DIPG), however, clinical efficacy remains limited. Here, the authors report that engineering B7-H3-targeting CAR T cells to express the chemokine receptor CXCR3-A enhances their trafficking and efficacy in DIPG preclinical models.
Resistance signaling in the tumor microenvironment limits CAR T cell therapy in solid tumors. This study introduces a multiplex engineered CAR T cell strategy using six gene edits to overcome multiple inhibitory barriers.
Solid tumors often resist immunotherapy due to an immunosuppressive tumor microenvironment. Here, the authors develop CancerPAM, a multiomics CRISPR pipeline that enables tumor-specific cytokine expression to boost immune infiltration and CAR T cell efficacy in neuroblastoma.
Components of the glycocalyx have been shown to impair immune cell functions, including of CAR-T cells. Here the authors show that CAR-T cell mediated cytotoxicity in pancreatic cancer models can be enhanced by incorporating non-signalling binding domains that target the glycocalyx.
Peritoneal metastasis remains a major clinical challenge due to the lack of effective therapeutic options. In this study, the authors present intraperitoneal programming of tailored chimeric antigen receptor macrophages (CAR-Ms) as a strategy against peritoneal metastasis.
Durable, multi-antigen CAR T responses in B-cell malignancies are in need. The authors here demonstrate that AI-guided CAR designs combined with targeted pathway modulation enhance persistence, prevent antigen escape, and improve anti-tumor efficacy.
T-cell therapies have huge potential but face technical limitations. Here, the authors report on a dextran-based nanoparticle platform that efficiently expands T cells, enhances CAR T-cell potency, persistence, and anti-tumour efficacy, using simpler and faster methods than current techniques.
CAR-T cell efficacy is often limited by the inability to maintain a memory T cell program. Here, the authors show that intrinsic CXCR4 expression enhances CAR-T cell persistence and memory differentiation in acute myeloid leukemia.