Methods of using interleukin-10 for treating diseases and disorders

A genetically modified T-cell transformed with a first nucleic acid sequence encoding a chimeric antigen receptor (CAR), wherein the CAR comprises:

• a) at least one antigen-specific targeting region that specifically binds a cell surface antigen present on the target cell population,
• b) a transmembrane domain, and
• c) an intracellular signaling domain,
• and a second nucleic acid sequence, wherein the second nucleic acid sequence comprises:
• a) a nucleic acid encoding a signal peptide (SP);
• and
• b) a nucleic acid encoding an IL-10 polypeptide
• the nucleic acid encoding the signal peptide being in frame with the nucleic acid sequence encoding the IL-10 polypeptide;
• wherein said first and second nucleic acid sequences are operably linked to at least one transcriptional and translational regulatory sequence capable of directing the transcription and translation of a nucleic acid sequence in the genetically modified T-cell, such that the genetically modified T-cell expresses the CAR and the IL-10 polypeptide encoded by said first and second nucleic acid sequences respectively.

A method of treating a mammalian subject having a cancer-related disease, disorder or condition, comprising administering to the subject a therapeutically effective amount of a genetically modified T-cell transformed with a first nucleic acid sequence encoding a chimeric antigen receptor (CAR), wherein the CAR comprises:

• a) at least one antigen-specific targeting region that specifically binds a cell surface antigen present on the target cell population,
• b) a transmembrane domain, and
• c) an intracellular signaling domain,
• and a second nucleic acid sequence, wherein the second nucleic acid sequence comprises:
• a) a nucleic acid encoding a signal peptide (SP);
• and
• b) a nucleic acid encoding an IL-10 polypeptide
• the nucleic acid encoding the signal peptide being in frame with the nucleic acid sequence encoding the IL-10 polypeptide;
• wherein said first and second nucleic acid sequences are operably linked to at least one transcriptional and translational regulatory sequence capable of directing the transcription and translation of a nucleic acid sequence in the genetically modified T-cell, such that the genetically modified T-cell expresses the CAR and the IL-10 polypeptide encoded by said first and second nucleic acid sequences respectively.