Abstract: Aspects of the present invention relate to the use of chemokine receptors such as e.g., CCR4 and CCR6, as homing agents. The chemokine receptor(s) is/are expressed by cells containing synthetic chromosomes. The chemokine receptor(s) is/are under controllable expression from a synthetic chromosome and can be used to control an immune response so as to treat or inhibit a disease such as cancer. The control is provided by inducing leukocyte trafficking to sites of disease. If more than one chemokine receptor is expressed, the levels can be individually controlled so that the desired cellular trafficking pattern can be obtained.

Abstract: Aspects of the present invention relate to synthetic chromosomes that may be incorporated into leukocytes, wherein the synthetic chromosomes comprise nucleic acid sequences encoding multiple Chimeric Antigen Receptors (CARs). Such manipulated leukocytes can be used in medicine, notably in the treatment of a cancer such as in the treatment of cancer having solid tumors. The leukocytes may be lymphocytes, including tumor-infiltrating lymphocytes. T cells. NK cells or B cells. In a preferred aspect, the leucocytes are syngeneic and T cells.

Abstract: Aspects of the present invention relate to the use the growth factors such as e.g., cytokines IL-2 and IL-12 for T-cell activation whereby the growth factor(s) is/are expressed by cells comprising synthetic chromosomes. The growth factor(s) is/are desirably under controllable expression from a synthetic chromosome. By approaches described herein, one can control an immune response to treat or inhibit a disease such as a cancer. The control may be provided by inducing expression of the growth factor(s), wherein expression level(s) can be fine-tuned. If more than one growth factor is expressed, the levels can be individually controlled so that the desired concentrations of each growth factor are obtained.