Publications by authors named "K Takesako"

Introduction: Adoptive cell transfer of genetically engineered T cells is a promising treatment for malignancies; however, there are few ideal cancer antigens expressed on the cell surface, and the development of chimeric antigen receptor T cells (CAR-T cells) for solid tumour treatment has been slow. CAR-T cells, which recognise major histocompatibility complex and peptide complexes presented on the cell surface, can be used to target not only cell surface antigens but also intracellular antigens. We have developed a CAR-T-cell product that recognises the complex of HLA-A*02:01 and an epitope of the MAGE-A4 antigen equipped with a novel signalling domain of human GITR (investigational product code: MU-MA402C) based on preclinical studies.

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  • * In a mouse study, T cells with CEA-specific CAR showed significant tumor reduction but caused weight loss in mice that express CEA, indicating possible off-target effects related to malnutrition rather than inflammation.
  • * The study highlights the balance between effective tumor treatment and managing side effects, suggesting that future CAR-T cell designs and treatment preparations should aim to minimize toxicity while preserving efficacy for patients with CEA-associated solid tumors.
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  • Preparative lymphodepletion, which temporarily reduces the immune system, may help enhance the effectiveness of T-cell therapy, but its necessity for TCR-engineered T-cell therapy is still uncertain.
  • A clinical trial was conducted with 10 patients suffering from recurrent esophageal cancer who received TCR gene-engineered T-cell transfers without any lymphocyte-depleting treatments or IL2 administration.
  • The results revealed that while some TCR-transduced cells persisted in the patients for extended periods, most showed tumor progression, indicating that T-cell persistence doesn’t always correlate with tumor regression and that other factors might influence treatment outcomes.
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Oncolytic virus therapy is a promising new therapeutic method, one of an eagerly anticipated class of biological therapies against cancer. There are many different classes of oncolytic virus. One of these, herpes oncolytic virus, is strongly oncolytic and has a large DNA genome as 150k bp.

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T cells express multiple integrin molecules. The significance of signaling through these molecules on acquisition of T-cell effector functions and memory formation capacity remains largely unknown. Moreover, the impact of stimulation through these signals on the generation of T cells for adoptive immunotherapy has not been elucidated.

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