Methods for developing disease-related nanobodies and related products and kits are provided. The disease-specific proteins are extracellular matrix (ECM) proteins, domains or epitopes that are associated with various aspects of disease and are not present, or are present in very low quantities, in non-diseased individuals. Highly effective nanobodies capable of specifically binding to these ECM protein epitopes useful in in vivo imaging assays, the detection, diagnosis and treatment of diseases as well as monitoring therapeutic progress in a patient with a disease are provided herein.

Compounds, compositions, and methods for use in inhibiting the E3 enzyme Cbl-b in the ubiquitin proteasome pathway are disclosed. The compounds, compositions, and methods can be used to modulate the immune system, to treat diseases amenable to immune system modulation, and for treatment of cells in vivo, in vitro, or ex vivo.

Provided are a preparation method of trophoblasts with limited generations, a culture method of SNK cells and a method for treating tumor. The preparation method of trophoblasts includes the following steps: ligating a TAX2 gene to a lentiviral expression vector, followed by transferring into competent cells to obtain a lentivirus containing the TAX2 gene; infecting PBMCs with the lentivirus containing the TAX2 gene and culturing, and collecting CD3-cells; ligating a 41BBL-MICA fusion gene to the lentiviral expression vector, followed by transferring into the competent cells to obtain a lentivirus containing the 41BBL-MICA fusion gene; and mixing the CD3-cells with the lentivirus containing the 41BBL-MICA fusion gene and culturing to obtain the trophoblasts with limited generations.

The present disclosure relates to an engineered immune cell and use thereof. The present disclosure provides an engineered immune cell comprising a CAR or engineered TCR, which CAR or engineered TCR can comprise a first antigen binding domain and a second antigen binding domain. The engineered immune cells of the present disclosure, when administered into a subject, can inhibit the host immune cells such as T cells and/or NK cells and enhance the survival and persistence of the engineered immune cells in vivo, thereby exhibiting more effective tumor killing activity.

This present disclosure relates to systems, methods, and compositions useful for profiling T cell receptor (TCR) and B cell receptor (BCR) repertoire using next-generation sequencing (NGS) methods. The present disclosure also relates to systems and methods for diagnosing, treating, or predicting infection, disease, medical conditions, therapeutic outcome, or therapeutic efficacy based on the TCR/BCR profile data from a subject in need thereof.

Embodiments of the disclosure include methods and compositions related to targeting of CD70-expressing cells with NK cells specifically engineered to bind the CD70 antigen. In particular embodiments, NK cells that are manipulated to expressing CD70-targeting engineered receptors, such as CARs, are utilized to target cancers that express CD70. In certain embodiments, vectors that express the CD70-targeting CARs also express particular a suicide gene and/or one or more particular cytokines.

This disclosure provides methods for producing multi-TCR T cells with enhanced anti-tumor phenotypes. The T cells are made from hematopoietic stem cells by introducing into the hematopoietic stem cells a first TCR and subsequently a second TCR.

Provided are engineered human immune cells, a preparation method, and an application thereof. The engineered human immune cells are immune killer lymphocytes induced by reprogramming human T cells, from which the BCL11B gene is deleted. The engineered human immune cells retain markers and functions of the T cells from which they are derived and have markers and functions of NK cells. The reprogrammed engineered human immune cells can be used to prepare drugs for treating tumors and infectious diseases.

Provided herein are populations of enriched ex vivo expanded umbilical cord blood-derived regulatory T cells. Also provided are methods of making and using the same.

Provided herein are methods for enhancing the transduction efficiency of vectors into cells, e.g., primary human T lymphocytes.