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-AB/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.

The present invention provides a method for increasing the sensitivity of a T cell expressing a cell-surface antibody to a target antigen, which comprises the step of lowering the affinity of the antibody to the target antigen by at least 100-fold. The invention also provides chimeric antigen receptor comprising an antibody domain having an affinity for antigen in the range 100-1 μM, its encoding nucleic acid sequence and uses thereof.

Several embodiments disclosed herein relate to methods and processes for the co-expansion of multiple types of immune cells, in order to generate a mixed cell population. Some embodiments relate to the use of various stimuli specific to the various subpopulations to achieve expansion of those subpopulations at a particular time in a culturing process in order to generate an expanded population of immune cells having a desired ratio of the various subpopulations. In several embodiments, such mixed cell populations exhibit desirable characteristics, such as cytotoxic effects against tumor cells that enhance the efficacy of cancer immunotherapy.

A serum free cell culture media, wherein the media is adapted to be conditioned by culturing a first set of eukaryotic cells in the media, wherein the first set of eukaryotic cells use an expression vector to excrete levels of desired complex proteins into the media; wherein said desired complex proteins include human Growth Hormone (hGH), Growth Hormone-like growth factors, insulin-like growth factors, insulin, modified insulins, cytokines, mitogenic proteases and mixtures thereof; and wherein the media is adapted to grow a set of eukaryotic cells.

Provided herein are ex vivo methods for the expansion of cord blood-derived natural killer cells and methods of their use. Examples of embodiments include stimulating mononuclear cells from cord blood in the presence of antigen presenting cells (APCs) and IL-2 and re-stimulating the cells with APCs to produce expanded NK cells. In specific embodiments, the method does not utilize human leukocyte antigen (HLA) matching.

The invention provides cell culture conditions for culturing stem cells, including feeder-free conditions for generating and culturing human induced pluripotent stem cells (iPSCs). More particularly, the invention provides a culture platform that allows long-term culture of pluripotent cells in a feeder-free environment; reprogramming of cells in a feeder-free environment; single-cell dissociation of pluripotent cells; cell sorting of pluripotent cells; maintenance of an undifferentiated status; improved efficiency of reprogramming; and generation of a naïve pluripotent cell.

Disclosed are methods of isolating a TCR having antigenic specificity for a mutated amino acid sequence encoded by a cancer-specific mutation, the method comprising: identifying one or more genes in the nucleic acid of a cancer cell of a patient, each gene containing a cancer-specific mutation that encodes a mutated amino acid sequence; inducing autologous APCs of the patient to present the mutated amino acid sequence; co-culturing autologous T cells of the patient with the autologous APCs that present the mutated amino acid sequence; selecting the autologous T cells; and isolating a nucleotide sequence that encodes the TCR from the selected autologous T cells, wherein the TCR has antigenic specificity for the mutated amino acid sequence encoded by the cancer-specific mutation. Also disclosed are related methods of preparing a population of cells, populations of cells, TCRs, pharmaceutical compositions, and methods of treating or preventing cancer.

The present disclosure provides methods for re-stimulating TIL populations that lead to improved phenotype and increased metabolic health of the TILs and provides methods of assaying for TIL populations to determine suitability for more efficacious infusion after re-stimulation.

Provided herein are methods for preparing and characterizing SARS-co2 antigen specific immune cell cultures and preparations and methods of using the same in adoptive immunotherapy for cancer, infections and immune disorders. Also, provided are compositions and methods for generating immune cells expressing synthetic antigen binding receptors targeting SARS-cov2 and methods of use of these cells for the treatment and prevention of COVID-19. Also provided are compositions and methods for determining immune response to SARs-cov2 in a subject, detecting SARS-cov2, measuring cytotoxicity induced by SARS-cov2, and detecting the expression and cytotoxicity of synthetic antigen binding receptors targeting SARS-cov2.

A method of expanding TCRalpha deficient T-cells by expressing pTalpha or functional variants thereof into said cells, thereby restoring a functional CD3 complex. This method is particularly useful to enhance the efficiency of immunotherapy using primary T-cells from donors. This method involves the use of pTalpha or functional variants thereof and polynucleotides encoding such polypeptides to expand TCRalpha deficient T-cells. Such engineered cells can be obtained by using specific rare-cutting endonuclease, preferably TALE-nucleases. The use of Chimeric Antigen Receptor (CAR), especially multi-chain CAR, in such engineered cells to target malignant or infected cells. The invention opens the way to standard and affordable adoptive immunotherapy strategies for treating cancer and viral infections.