The invention disclosed herein relates to improved methods for expanding cell populations, particularly B cell populations. The invention further relates to improved B-cell expansion media, compositions comprising expanded B cells and methods of using such expanded B cells. The invention further relates to methods of treating diseases or disorders wherein a population of B cells is obtained and cultured, and wherein said B cells are engineered to express a payload and/or a chimeric receptor, and wherein said B cells are administered to a subject.

In certain aspects, the present invention provides methods for inducing a stable gene modification of a target nucleic acid via homologous recombination in a primary cell, such as a primary blood cell and/or a primary mesenchymal cell. In certain other aspects, the present invention provides methods for enriching a population of genetically modified primary cells having targeted integration at a target nucleic acid. The methods of the present invention rely on the introduction of a DNA nuclease such as a Cas polypeptide and a homologous donor adeno-associated viral (AAV) vector into the primary cell to mediate targeted integration of the target nucleic acid. Also provided herein are methods for preventing or treating a disease in a subject in need thereof by administering to the subject any of the genetically modified primary cells or pharmaceutical compositions described herein to prevent the disease or ameliorate one or more symptoms of the disease.

The present invention is directed to a method of generating multilineage potential cells by de-differentiation of somatic leukocytes in a mixed leukocyte suspension from a blood sample. The present invention is also directed to the use of the generated multilineage potential cells to treat conditions in humans and mammals.

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.

Disclosed are methods of treating Acute Respiratory Distress Syndrome using B cells, e.g., by administering B cells to a subject in need thereof.

A non-human mammalian model for human diseases or disorders comprising a non-human neutrophil depleted mammalian host engrafted with a human skin equivalent (huSE) and human immune cells.

The present invention provides an ex vivo lymph node is provided. The ex vivo lymph node comprises an intact lobule in a chamber connected to an afferent lymphatic vessel and an efferent lymphatic vessel. The intact lobule is perfused with a lymphatic fluid into the chamber via the afferent lymphatic vessel and out of the chamber via the efferent lymphatic vessel and perfused with a vascular fluid into the intact lobule via an endogenous artery and out of the intact lobule via an endogenous vein. Also provided is a method for preparing the ex vivo lymph node. Further provided are methods for screening for an agent capable of changing the ex vivo lymph node, producing T lymphocytes or B lymphocytes and determining immunoreactivity of the ex vivo lymph node.

In some embodiments, compositions and methods re¬lating to isolated artificial antigen presenting cells (aAPCs) are dis¬closed, including aAPCs comprising a myeloid cell transduced with one or more viral vectors, such as a MOLM-14 or a EM-3 myeloid cell, wherein the myeloid cell endogenously expresses HLA-A/B/C, ICOS-L, and CD58, and wherein the one or more viral vectors com¬prise a nucleic acid encoding CD86 and a nucleic acid encoding 4-1BBL and/or OX40L and transduce the myeloid cell to express CD86 and 4-1BBL and/or OX40L proteins. In some embodiments, methods of expanding tumor infiltrating lymphocytes (TILs) with aAPCs and methods of treating cancers using TILs after expansion with aAPCs are also disclosed.

Provided is a fusion protein comprising IL-2 protein and CD80 protein, a fusion protein having a high content of sialic acid, and a pharmaceutical composition containing same. A fusion protein containing CD80 fragment, immunoglobulin Fc, and an IL-2 variant can activate immune cells, such as natural killer cells, and at the same time, can control immune cell regulatory activity of regulatory T cells. In addition, the fusion protein having a high content of sialic acid can proliferate immune cells, such as lymphocytes including CD8+ T cells and natural killer cells. Therefore, a pharmaceutical composition containing the fusion protein as an active ingredient is very industrially useful in that such pharmaceutical composition can increase immune activity in the body, and thus can be effectively used against infectious diseases as well as cancer.

The present application provides a group of human immortalized B lymphocyte cell lines and use thereof, and specifically provides a combination of four closely related immortalized lymphocyte cell lines. The combination can be used as a reference substances for measuring the performance of a detection platform. When the four closely related immortalized lymphocyte cell lines are used as reference substances for epigenome, transcriptome, proteome, and metabolome, an intrinsic magnitude difference gradient can be formed to evaluate the sensitivity of histological detection.