The present disclosure relates to compositions including molecules of modified mRNA encoding GATA Binding Protein 4, modRNA encoding Myocyte Enhancer Factor 2C, modRNA encoding T-box 5, modRNA encoding Heart- and neural crest derivatives-expressed protein 2, modRNA encoding dominant negative transforming growth factor beta, and modRNA encoding domimant negative Wingless-related integration site 8a, wherein said molecules of modRNAs are present in said composition in a ratio. The present disclosure further relates to pharmaceutical compositions, methods for increasing a ratio of a number of cardiomyocytes to a number of non-cardiomyocytes within a population of cells, methods for treating cardiac injury, methods for stimulating vascular regeneration, methods for treating of stroke, and methods for enhancing wound healing.

The current invention reports the use of meta-tyrosine for increasing the specific productivity of a eukaryotic cell that produces/expresses a polypeptide. In the current method it is not necessary to perform a temperature-, osmolality- or pH shift or to add drugs like valproic acid or sodium butyrate to modulate the specific productivity of the cultivated cells. The method does not affect cell viability or product titer.

The present invention is directed to the field of immunotherapy. Specifically, the invention provides compositions and methods for improved T cell modulation ex vivo and in vivo and for the treatment of cancer and other pathologies. More specifically, embodiments of the invention are directed to the use of soluble NTB-A polypeptides or agonists thereof for the treatment of cancer patients, for preventing and treating cytopenia in susceptible patients, and for the ex vivo preparation of improved cell compositions.

The present invention provides improved and/or shortened processes and methods for reprogramming TILs in order to prepare therapeutic populations of TILs with increased therapeutic efficacy. Such reprogrammed TILs find use in therapeutic treatment regimens.

A method of treating a patient who has hepatocellular carcinoma (HCC), colorectal carcinoma (CRC), glioblastoma (GB), gastric cancer (GC), esophageal cancer, NSCLC, pancreatic cancer (PC), renal cell carcinoma (RCC), benign prostate hyperplasia (BPH), prostate cancer (PCA), ovarian cancer (OC), melanoma, breast cancer (BRCA), CLL, Merkel cell carcinoma (MCC), SCLC, Non-Hodgkin lymphoma (NHL), AML, gallbladder cancer and cholangiocarcinoma (GBC, CCC), urinary bladder cancer (UBC), and uterine cancer (UEC) includes administering to said patient a composition containing a population of activated T cells that selectively recognize cells in the patient that aberrantly express a peptide. A pharmaceutical composition contains activated T cells that selectively recognize cells in a patient that aberrantly express a peptide, and a pharmaceutically acceptable carrier, in which the T cells bind to the peptide in a complex with an MHC class I molecule, and the composition is for treating the patient who has HCC, CRC, GB, GC, esophageal cancer, NSCLC, PC, RCC, BPH, PCA, OC, melanoma, BRCA, CLL, MCC, SCLC, NHL, AML, GBC, CCC, UBC, and/or UEC. A method of treating a patient who has HCC, CRC, GB, GC, esophageal cancer, NSCLC, PC, RCC, BPH, PCA, OC, melanoma, BRCA, CLL, MCC, SCLC, NHL, AML, GBC, CCC, UBC, and/or UEC includes administering to said patient a composition comprising a peptide in the form of a pharmaceutically acceptable salt, thereby inducing a T-cell response to the HCC, CRC, GB, GC, esophageal cancer, NSCLC, PC, RCC, BPH, PCA, OC, melanoma, BRCA, CLL, MCC, SCLC, NHL, AML, GBC, CCC, UBC, and/or UEC.

Peptides have immune system modulation properties. The immunologically active peptides can be derived from the heavy-chain complementarity determining region-3 of a humanized monoclonal antibody to NaPi2B transporter. Such peptides can be used to modulate the immune system of a subject under cancer treatment.

Disclosed herein are chimeric antigen receptors (“CARs”) comprising an antigen binding site that recognizes citrullinated polypeptides. Citrullinated polypeptides, such as citrullinated vimentin, fibrinogen, and filaggrin, are expressed in the synovium of subjects with rheumatoid arthritis. Further disclosed are T cells, and in particular, Treg cells, that express these CARs. Administration of these CAR-T cells is useful in the treatment of rheumatoid arthritis as well as other diseases associated with citrullinated peptides.

The present invention relates to cell culture media supplements or complete media compositions comprising plant-produced heterologous recombinant human albumin, as well as methods of making the cell culture media, and methods of using the supplemented cell culture media to improve viability, productivity, and growth characteristics of cultured cells.

The present invention relates to improvement of the yield of skin-derived pluripotent precursor cells in induction of differentiation of stem cells to skin-derived pluripotent precursor cells. The present invention provides a method for preparing skin-derived pluripotent precursor cell comprising culturing a neural crest stem cells in the presence of at least one selected from the group consisting of laminin and a fragment thereof to differentiate the cells to skin-derived pluripotent precursor cells, wherein the laminin is at least one selected from the group consisting of laminin 111, laminin 121, laminin 332, laminin 421, laminin 511, laminin 521, and a variant thereof.

The invention relates to a new process for manufacturing in vitro antigen-specific T lymphocytes (CellTrAg), marked with intracellular dye and expanded in the presence of monocytes loaded with the antigen and subsequently sorted based on the low intensity of intracellular dye where the low intensity of fluorescence is a marker of antigen-specificity in that a loss of fluorescence correlated with the intensity of proliferation. The antigen specificity is assessed in functional tests in which antigen-specific lymphocytes sorted on the basis of low fluorescence are more active than non-specific lymphocytes with high fluorescence during sort; activity is defined in the case of regulatory T lymphocytes as inhibition of effector lymphocyte function and in the case of T effector lymphocytes as enhancing the characteristics of these cells such as proliferation, production of cytokines and cytotoxic factors.