Methods and composition for production of T cells are provided. Also provided are therapeutic methods using engineered T cells. For example, in certain aspects methods include preparing three dimensional cell culture compositions comprising stroma cells and hematopoietic stem or progenitor cells in a serum-free medium for producing T cells.

Compositions and methods described in this document make use of macrophage-derived engineered vesicles (MEV) having specificity for delivery to a target environment, for use in modifying macrophage phenotype and/or treating a condition.

Provided is a serum-free formula for T cell expansion, which comprises a basal serum-free medium and a cytokine combination, and the cytokine combination comprises IL-2, IL-4, IL-7, IL-10 and IL-15; wherein, based on a total volume of the basal serum-free medium, a content of IL-2 is from 5 ng/ml to 50 ng/ml, a content of IL-4 is from 5 ng/ml to 200 ng/ml, a content of IL-7 is from 5 ng/ml to 90 ng/ml, a content of IL-10 is from 5 ng/ml to 50 ng/ml and a content of IL-15 is from 5 ng/ml to 200 ng/ml. The serum-free formula for T cell expansion can exert the effects of expanding T cells, especially selectively expanding the CD3.sup.+CD8.sup.+ T cells, under a serum-free circumstance, thereby avoiding the uncertainty and the risks derived from the animal serum and promoting the development of adoptive cell therapy or immunotherapy.

The subject invention pertains to a novel method for treating Peripheral Arterial Disease (PAD) by leveraging the angiogenic potential of type 2 cytokines IL-4 and IL-13 to enhance the efficacy of induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) and induced endothelial cells derived from fibroblasts (iECs). This present invention aims at enhancing the muscle regeneration and revascularization for obese and diabetes individuals.

In some embodiments, methods of delivering a therapeutically effective amount of an expanded number of tumor infiltrating lymphocytes obtained from tumor remnants to a patient in need thereof, for the treatment of a cancer, are disclosed.

The present invention provides compositions comprising chimeric receptors, including chimeric costimulatory receptors (CCRs), and/or chemokine receptors, methods for preparing CCRs and/or chemokine receptors, and therapeutic populations of tumor infiltrating lymphocytes, marrow infiltrating lymphocytes, and peripheral blood lymphocytes expressing CCRs and/or chemokine receptors with increased therapeutic performance and other advantages for the treatment of cancers, including solid tumor cancers.

The present invention relates to an accelerated method to generate high yields of type-1 polarizing mRNA loaded dendritic cells for use in immunotherapy, and in particular for use in cancer vaccination.

An in vitro expansion process for rapid expansion of antigen specific T cells, such as allogeneic antigen specific T cells comprising the steps culturing in a gas permeable vessel a population of PBMCs (such as allogeneic PBMCs) in the presence of antigen, for example a peptide or peptide mix relevant to a target antigen(s), in the presence of an exogenous cytokine characterized in that the expansion to provide the desired population of T cells is 14 days or less, or example 9, 10, 11 or 12 days, such as 10 days. The disclosure also extends to T cell populations generated by and obtained from the method and the use of same in therapy.

There is provided inter alia according to the invention an ex vivo method of obtaining tolerogenic antigen presenting cells (APCs) that have the capability to induce tolerance in the immune system to an antigen, the method comprising (a) isolating monocytes from a sample obtained from a mammal; and (b) culturing the isolated monocytes in a cell culture to induce differentiation of the monocytes into antigen presenting cells having a tolerogenic phenotype, wherein the cell culture comprises (i) retinoic acid and TGFbeta, (ii) retinoic acid, TGFbeta and an AhR agonist or (iii) retinoic acid and an AhR agonist.

Disclosed herein are micropatterned surfaces, particularly in the shape of micro-brushes having a base and a plurality of elongated elements. The micropatterned surfaces suitably biofunctionalized are particularly useful for activation and expansion of cells. Methods for activation and expansion of cytotoxic lymphocytes with decreased exhaustion potential are also provided, as well as means involving same to treat a patient in need thereof.