The present document describes compounds, or pharmaceutically acceptable salt thereof, of a core formula (I) Wherein R1 includes an amino group. These compounds are particularly useful in the formulation and in vivo and ex vivo delivery of nucleic acid and protein therapeutics for preparing and implementing T cell transfection, gene editing, cancer therapies, cancer prophylactics, and in the preparation of vaccines.

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The present invention relates to an immune cell, which contains a TMEM59 protein and/or a functional fragment thereof, a chimeric antigen receptor (CAR) and/or a coding element thereof, as well as a use of the immune cell in the preparation of a drug for treating tumors. Further provided are a method for promoting the proliferation of immune cells and a method for promoting the production of memory cells.

The disclosure provides methods of treating a malignancy comprising administering an effective dose of an immune cell therapy (e.g., a chimeric antigen receptor genetically modified T cell immunotherapy) and methods for manufacturing such immunotherapy. Some aspects of the disclosure relate to methods of determining objective response of a patient to an immune cell immunotherapy based on the levels of patient and product attributes prior to and after administration of the immunotherapy to the patient.

The present invention aims to solve a problem in T-cell transfer therapy and the like, which is T-cell exhaustion, and to provide a technique to enhance T cell activity. T cells having cell surface markers of CD45RA.sup.+ and CCR7.sup.+ can be produced by culturing activated T cells in the presence of (a) a conditioned medium derived from stromal cells or (b) CXCL12.

Provided are methods for determining the risk of toxicity (e.g., neurotoxicity) and/or the likelihood of response to a cell therapy. In some aspects, the methods generally involve assessing parameters or biomarkers (e.g., blood analytes) that are associated with toxicity and/or response. In some aspects, the methods relate to adoptive cell therapy involving the administration of doses of cells for treating subjects with certain B cell malignancies, such as chronic lymphocytic leukemia (CLL), such as relapsed or refractory CLL, or small lymphocytic lymphoma (SLL). The cells for the adoptive cell therapy generally express recombinant receptors such as chimeric antigen receptors (CARs). In some aspects, the methods can be used to identify or select subjects for treatment, for example, with a cell therapy.

Provided are a chimeric antigen receptor capable of targeting B7-H3, a nucleic acid molecule encoding the chimeric antigen receptor, a nucleic acid construct comprising the nucleic acid molecule, an immune effector cell expressing the chimeric antigen receptor, and use thereof. The chimeric antigen receptor comprises an anti-B7-H3 binding domain, a hinge region, a transmembrane domain and a signal transduction domain. Further provided are a composition and a method for diagnosing, treating or preventing tumors that express B7-H3.

Disclosed herein are circular RNA s and transfer vehicles, along with related compositions and methods of treatment. The circular RNAs can comprise group I intron fragments, spacers, an IRES, duplex forming regions, and/or an expression sequence, thereby having the features of improved expression, functional stability, low immunogenicity, ease of manufacturing, and/or extended half-life compared to linear RNA. Pharmaceutical compositions comprising such circular RNAs and transfer vehicles are particularly suitable for efficient protein expression in immune cells in vivo. Also disclosed are precursor RNAs and materials useful in producing the precursor or circular RNAs, which have improved circularization efficiency and/or are compatible with effective circular RNA purification methods.

Provided is an engineered T cell. A polypeptide down-regulating the expression of a TCR/CD3 complex on cell surface is introduced to reduce the expression of the TCR/CD3 complex on the cell surface. The engineered T cell can be used for therapeutic purposes, such as cancer treatment.

A method for purifying a universal human CAR-T cell, comprising: (i) destroying, by using gene editing technology, a TRAC gene region from position 23016448 to position 23016490 of chromosome 14 and a B2M gene region from position 45003745 to position 4500378 of chromosome 15 in the human CAR-T cell; (ii) then introducing a mRNA targeting TCRα/β into the gene-edited CAR-T cell; and (iii) in vitro culturing the CAR-T cell population after the described treatment.

The invention provides improved methods for adoptive cell therapies for the treatment of cancer.