The present invention provides improved methods for expanding TILs and producing therapeutic populations of TILs, including methods for gene-editing at least a portion of the TILs to enhance their therapeutic efficacy. The methods lead to improved efficacy, improved phenotype, and increased metabolic health of the TILs in a shorter time period, while allowing for reduced microbial contamination as well as decreased costs. Such TILs find use in therapeutic treatment regimens.

The present invention relates to compositions of extracellular vesicles (EVs) which are characterized by a strong proangiogenic activity and are effective in the therapeutic treatment of ischemic diseases and ischemic injuries or in wound healing. The extracellular vesicles (EVs) suitable for use in the compositions of the invention are either derived from a blood component or are selected by means of a potency test for pro-angiogenesis. Also disclosed is a method of manufacturing a pharmaceutical preparation of extracellular vesicles (EVs) characterized by a strong proangiogenic activity.

Methods of producing stem cell conditioned media to treat mammalian injuries or insults. In at least one embodiment of a method of producing a stem cell conditioned media of the present disclosure, the method comprises the steps of culturing at least one stem cell in a first cell culture medium, replacing some or all of the first cell culture medium with a second cell culture medium and further culturing the at least one stem cell in the second cell culture medium, and collecting a quantity of the second cell culture medium after a culture duration, wherein the quantity of the second cell culture medium contains a cell culture byproduct effective to treat a mammalian insult or injury.

A conditioned cell culture medium of CD11b.sup.low human macrophages or a biologically active fraction thereof can be prepared by a method that includes (i) culturing a population of human mononuclear cells of the monocyte/macrophage lineage for 5-7 days, so as to induce differentiation of the mononuclear cells to macrophages; (ii) incubating the macrophages obtained in (i) with apoptotic cells or in the presence of a pro-resolving lipid mediator to reduce the CD11b expression, thus obtaining a culture of CD11b.sup.low macrophages; and (iii) collecting the conditioned cell culture medium of CD11b.sup.low macrophages. Pharmaceutical compositions containing the CD11b.sup.low macrophages conditioned medium or a culture of CD11b.sup.low macrophages can be used in the treatment of cancer or fibrosis.

Disclosed herein are bioreactor systems and methods of utilizing said systems.

The present invention relates to the field of biomedicine, and in particular to an engineered migrasome, a method for preparing the engineered migrasome, a delivery system comprising the engineered migrasome, and a method for preparing the delivery system.

Disclosed herein are bioreactor systems and methods of utilizing said systems.

The present disclosure relates to NK cells expressing dual-targeting chimeric antigen receptors for CD19 and CD22 and uses thereof, and more particularly, to a method for producing CAR-NK cells targeting CD19 and CD22, and a pharmaceutical composition for preventing or treating a disease mediated by B cells comprising a CAR-NK cell produced by the method. The present CAR-NK cells can be usefully utilized as a composition for preventing or treating diseases related to CD22 (or CD19) expression or diseases related to B cells.

Methods are disclosed for treating a subject with a tumor. These methods include administering to the subject a therapeutically effective amount of CD8.sup.+CD39.sup.+CD103.sup.+ T cells. Methods also are disclosed for isolating a nucleic acid encoding a T cell receptor (TCR) that specifically binds a tumor cell antigen. These methods include isolating CD8.sup.+CD39.sup.+CD103.sup.+ T cells from a sample from a subject with a tumor expressing the tumor cell antigen, and cloning a nucleic acid molecule encoding a TCR from the CD8.sup.+CD39.sup.+CD103.sup.+ T cells. In addition, methods are disclosed for expanding CD8.sup.+CD39.sup.+CD103.sup.+ T cells. In additional embodiments, methods are disclosed for determining if a subject with a tumor will respond to a checkpoint inhibitor. The methods include detecting the presence of CD8.sup.+CD39.sup.+CD103.sup.+ T cells in a biological sample from a subject.

Disclosed are methods for expanding tumor infiltrating lymphocytes (TILs) and driving TILs towards a memory T cell phenotype. Also disclosed is the creation of a mouse model to investigate adoptive cell therapy using TILs.