A three-dimensional (3D) lymphoid tissue model is provided, the model including a cellularized stromal compartment and a plurality of cellularized compartments including lymphocytes disposed within the stromal compartment; and a controlled fluid perfusion system configured to perfuse the model with a perfusion fluid. Methods of fabricating a 3D lymphoid tissue model and producing antibodies with the 3D lymphoid tissue model are also provided.

The present disclosure relates to the in vitro differentiation of memory B cells to plasmablasts or plasma cells and genetic modification of these cells to express a protein of interest, such as a specific antibody or other protein therapeutic.

In some embodiments, marrow-infiltrating lymphocytes (“MILs”) comprising a chimeric antigen receptor (“CAR”) are provided. In some aspects, the embodiments relate to a method for making a recombinant MIL, comprising obtaining bone marrow comprising MILs; and transfecting, transforming, or transducing the MILs with a nucleic acid encoding a chimeric antigen receptor. In some aspects, the embodiments relate to a method for treating a condition in a subject, comprising administering to the subject a MIL comprising a CAR.

Described herein are methods for selecting lymphocytes for adoptive cell therapy based on P-glycoprotein expression and compositions comprising same.

The present technology comprises methods for regulating an the immune system, and in particular methods for the regulation of a specific immune response, including the regulation of lymphocyte activity. Methods of the present technology comprise both the negative and positive modulation of CEACAM1 protein function.

An organ-on-a-chip microfluidic device is disclosed that mimics a human lymph node and/or human lymphoid tissue. The device can include cells from human blood and lymphatic tissue, include an extracellular matrix for the development of immune system components, and provide for the perfusion of fluids and solids resembling blood and lymphatic fluid within micrometer sized channels.

According to a first aspect of the invention, a method for the generation of a cell line is provided, comprising the steps of (a) providing a plurality of mammalian B cells, wherein each of the plurality of B cells comprises a transgenic genomic DNA sequence encoding a marker protein inserted into an endogenous immunoglobulin locus comprised in said B cell, and wherein the transgenic genomic DNA sequence is amenable to cleavage by a site directed nuclease, particularly Cas9; (b) replacing the transgenic genomic DNA sequence encoding a marker protein with a second transgenic DNA sequence encoding a protein of interest; (c) sorting B cells based on the presence or absence of the marker protein; and (d) collecting B cells in which the marker protein is absent.

According to a first aspect of the invention, a method for the generation of a cell line is provided, comprising the steps of (a) providing a plurality of mammalian B cells, wherein each of the plurality of B cells comprises a transgenic genomic DNA sequence encoding a marker protein inserted into an endogenous immunoglobulin locus comprised in said B cell, and wherein the transgenic genomic DNA sequence is amenable to cleavage by a site directed nuclease, particularly Cas9; (b) replacing the transgenic genomic DNA sequence encoding a marker protein with a second transgenic DNA sequence encoding a protein of interest; (c) sorting B cells based on the presence or absence of the marker protein; and (d) collecting B cells in which the marker protein is absent.

The present invention is directed to a method for the cultivation, optionally activation and growth of lymphocytes (T-, B- and NK-cells) by culturing these cells in a suitable cell growth medium on a nanoporous substrate having a pore diameter in the range of about 100 to 500 nm, optionally about 150 to 250 nm.

In some embodiments, compositions and methods relating to isolated artificial antigen presenting cells (aAPCs) are disclosed, 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 comprise 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.