The invention provides improved T cell compositions and methods for manufacturing T cells. More particularly, the invention provides methods of T cell manufacturing that result in adoptive T cell immunotherapies with improved survival, expansion, and persistence in vivo.

A method of producing helper T cells, comprising: (i) culturing T cells, which have been induced from pluripotent stem cells and into which a CD4 gene or a gene product thereof has been introduced, in a medium containing IL-2 and IL-15; and (ii) isolating CD40L-highly expressing T cells from cells obtained in step (i).

A therapeutic molecule (single chain-based antibody or ligand-based) optimized for expression and secretion from engineered T cells, which may be gamma delta (gd) T cells. When expressed from engineered gdT cells, the STAR will be secreted and mediate engagement between gdT cells and antigen/receptor on target cells. Binding mediates the formation of a cytolytic synapse between the gdT cell and the target cell leading to activation the gdT cells to release proteolytic enzymes that kill target cells.

The present invention relates to a chimeric costimulatory antigen receptor (CoStAR) useful in adoptive cell therapy (ACT), and cells comprising the CoStAR. The CoStAR can act as a modulator of cellular activity enhancing responses to defined antigens. The present invention also provides CoStAR proteins, nucleic acids encoding the CoStAR and therapeutic uses thereof.

The invention relates to a method of isolating a T cell that expresses a T cell receptor capable of binding specifically to an antigen presented by a cancer cell in association with an MR1 molecule. The method comprises the steps of (a) providing a preparation of T cells, (b) contacting the preparation with cancer cells expressing MR1 protein; (c) isolating a T cell that is specifically reactive to said cancer cells. The invention further relates to a method of preparing a T cell preparation expressing select MR1 recognizing T cell receptors from transgene expression vectors, the use of such T cell preparations in treatment of cancer, and to collections of MR1 reactive T cell receptor encoding nucleic acids and cells.

The present invention is targeted towards reinvigorating exhausted Tumor Infiltrating Lymphocytes (TILs) in vitro by co-culturing excised TIL containing tumor fragments with checkpoint inhibitors, stimulating the TILs with other interleukins known to revert T cell exhaustion), and/or inhibiting the effect of regulatory T cells secreted factors (such as IL-10) thereby creating a favorable tumor microenvironment (TME) where exhausted T-cells can expand faster and to higher numbers than currently established TIL expansion protocols.

The present invention relates to a method for effectively proliferating regulatory T cells, by which, particularly, in the presence of a fusion protein dimer comprising IL-2 protein or a variant thereof and CD80 protein or a fragment thereof, CD4+, CD25+, and CD127− T cells can be effectively proliferated. In particular, when combined with a predetermined cell culture medium, regulatory T cells such as CD4+, CD25+, and CD127− can be effectively and specifically proliferated. In addition, when the method is used, it has been confirmed that the survival rate of regulatory T cells is remarkably increased as compared to a conventionally used culture method using IL-2, and a significant increase in the yield of Foxp3+ regulatory T cells has been confirmed. Thus, such a proliferation method can be used in the field of cell therapeutic agents using regulatory T cells.

The present invention relates to a composition for proliferating a T cells, containing a fusion protein dimer comprising IL-2 protein or a variant thereof and CD80 protein or a fragment thereof, and to a method for culturing T cells using same. The T cells cultured according to the present invention increase the proliferation and activity of T cells even without using CD3/CD28 antibody-bound magnetic beads and proliferate T cells by culturing a patient's own peripheral blood mononuclear cells and are not likely to cause side effects in the human body, and thus will be widely used as a novel T cell therapeutic agent. Furthermore, in the case of CD8+ T cells cultured as described above, the activity thereof increases, and thus, the CD8+ T cells can be used as a more effective therapeutic agent.

Disclosed herein are compositions and methods to decellularize an isolated organ or portion thereof. Also disclosed herein are compositions and methods for treatment of disease utilizing a decellularized or recellularized organ. Also disclosed herein are methods of improving decellularization and/or recellularization of an isolated organ or portion thereof.

The present invention relates to novel method of generating “Lympho-Myeloid Niches (LMN)” from peripheral blood mononuclear cell (PBMC). The present invention relates to a method of generating macrophages, myeloid cells and T cell from Lympho-Myeloid Niches (LMN). The present invention also describes its application for developing novel cell based therapies, gene therapies, gene edited therapies for the treatment of various disease conditions using the Lympho-Myeloid Niches (LMN), and/or the cells generated from Lympho-Myeloid Niches (LMN) or their culture.