公开(公告)号：US20210161971A1

公开(公告)日：2021-06-03

申请号：US16621490

申请日：2018-06-12

Applicant: Sinai Health System

Inventor： Andras NAGY ,  Jeffrey HARDING ,  Kristina NAGY

IPC: A61K35/545 ,  C12N5/0735 ,  A61K45/06 ,  C07K14/705 ,  C07K14/52 ,  C07K14/47 ,  A61P37/06 ,  A61P27/02 ,  A61P25/16 ,  A61P9/10 ,  A61P19/02 ,  A61P3/10 ,  A61P7/04 ,  A61P3/00 ,  A61P1/16

Abstract: A cell genetically modified to comprise at least one mechanism for providing a local immunosuppression at a transplant site when transplanted in an allogeneic host, and methods for making and using the same are provided. The cell comprises a set of transgenes, each transgene encoding a gene product that is cytoplasmic, membrane bound, or local acting, and whose function is one or more of: to mitigate antigen presenting cell activation and function; to mitigate graft attacking leukocyte activity or cytolytic function; to mitigate macrophage cytolytic function and phagocytosis of allograft cells; to induce apoptosis in graft attacking leukocytes; to mitigate local inflammatory proteins; and to protect against leukocyte-mediated apoptosis. The transgenes comprise two or more of the following genes: PD-L 1, HLAG or H2-M3, Cd47, Cd200, FASLG or Fasl, Ccl21 or Ccl21b, Mfge8, and Serpin B9 or Spi6.

公开(公告)号：US20220016181A1

公开(公告)日：2022-01-20

申请号：US17413314

申请日：2019-12-13

Applicant: Sinai Health System

Inventor： Andras NAGY ,  Jeffrey HARDING ,  Kristina NAGY

IPC: A61K35/545 ,  A61K45/06 ,  C07K14/705 ,  C07K14/47 ,  C07K14/81 ,  C07K14/52 ,  A61P37/06

Abstract: Featured are cells and methods of use thereof for modulating an antigen-specific immune response in a subject. The cells comprise a set of transgenes comprising two or more of PD-L1, HLA-G or H2-M3, Cd47, Cd200, FASG or FasL, Ccl21 or Ccl21b, MfgeS and Serpin B9 or Spi6, that shield the cells from immune surveillance (ie. “cloaking genes”). The cells can be used to induce immune tolerance to an antigen (e.g., a donor alloantigen or a self-antigen), or to induce an immune response to (e.g., induce the production of antibodies directed against) a non-self antigen.