iPSC-derived hypoimmunogenic tissue resident memory T cells mediate robust anti-tumor activity against cervical cancer.

Functionally rejuvenated human papilloma virus-specific cytotoxic T lymphocytes (HPV-rejTs) generated from induced pluripotent stem cells robustly suppress cervical cancer. However, autologous rejT generation is time consuming, leading to difficulty in treating patients with advanced cancer. Although use of allogeneic HPV-rejTs can obviate this, the major obstacle is rejection by the patient immune system.

Establishment of ganglioside GD2-expressing extranodal NK/T-cell lymphoma cell line with scRNA-seq analysis.

Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKL), is characterized by Epstein-Barr virus infection and poor prognosis. We established a novel cell line, ENKL-J1, from bone marrow cells of an ENKL patient. We found that ENKL-J1 cells express the ganglioside GD2 (GD2) and that GD2-directed chimeric antigen receptor T cells exhibit cytotoxicity against ENKL-J1 cells, indicating that GD2 would be a suitable target of GD2-expressing ENKL cells.

Dual-antigen targeted iPSC-derived chimeric antigen receptor-T cell therapy for refractory lymphoma.

We generated dual-antigen receptor (DR) T cells from induced pluripotent stem cells (iPSCs) to mitigate tumor antigen escape. These cells were engineered to express a chimeric antigen receptor (CAR) for the antigen cell surface latent membrane protein 1 (LMP1; LMP1-CAR) and a T cell receptor directed to cell surface latent membrane protein 2 (LMP2), in association with human leucocyte antigen A24, to treat therapy-refractory Epstein-Barr virus-associated lymphomas. We introduced LMP1-CAR into iPSCs derived from LMP2-specific cytotoxic T lymphocytes (CTLs) to generate rejuvenated CTLs (rejTs) active against LMP1 and LMP2, or DRrejTs.

iPSC-Derived Neoantigen-Specific CTL Therapy for Ewing Sarcoma.

The prognosis of Ewing sarcoma caused by fusion is poor, especially after metastasis. Although therapy with CTLs targeted against altered EWS/FLI1 sequences at the gene break/fusion site may be effective, CTLs generated from peripheral blood are often exhausted because of continuous exposure to tumor antigens. We addressed this by generating induced pluripotent stem cell (iPSC)-derived functionally rejuvenated CTLs (rejT) directed against the neoantigen encoded by the fusion gene.

Sustainable Tumor-Suppressive Effect of iPSC-Derived Rejuvenated T Cells Targeting Cervical Cancers.

Immunotherapy utilizing induced pluripotent stem cell (iPSC) technology has great potential. Functionally rejuvenated cytotoxic T lymphocytes (CTLs) can survive long-term as young memory T cells in vivo, with continuous tumor eradication. Banking of iPSCs as an unlimited "off-the-shelf" source of therapeutic T cells may be feasible.

Dasatinib-induced anti-leukemia cellular immunity through a novel subset of CD57 positive helper/cytotoxic CD4 T cells in chronic myelogenous leukemia patients.

Dasatinib induces lymphocytosis of large granular lymphocytes (LGLs) in a proportion of patients with chronic myelogenous leukemia (CML), and is associated with better clinical outcomes. LGLs consist of cytotoxic T lymphocytes and natural killer cells; however, the context and phenotypic/functional features of each type of LGL are unknown. To better define features of these LGLs, we investigated lymphocytosis in CML patients treated with dasatinib.