Precursory regulatory cytotrophoblast cells and uses thereof
Inventors
Lee, Jau-Nan • Lee, Yuta • LEE, Tony Tung-Yin
Assignees
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Publication Number
US-11085019-B2
Publication Date
2021-08-10
Expiration Date
Abstract
Disclosed herein are precursory regulatory cytotrophoblast cells produced in vitro and compositions thereof. Also disclosed herein are methods of treating a disorder or condition by utilizing the cells disclosed herein.
Core Innovation
An in vitro-produced, isolated precursory regulatory cytotrophoblast (prCTB) and a prCTB cell population are provided with defined expression of immune-, checkpoint-, and apoptosis-related markers. The prCTB expresses beta-hormone human chorionic gonadotropin (β-hCG), human leukocyte antigen G (HLA-G), CD56, programmed death-ligand 1 (PD-L1), apoptosis signal receptor (Fas), Fas Ligand (FasL), insulin, heat shock protein 90 (HSP90), IL-15, and leukocyte immunoglobulin-like receptor subfamily B members (LILRB1, LILRB2).
The prCTB lacks expression of programmed cell death protein 1 (PD-1) while expressing selected pro-survival and apoptosis-regulatory proteins. The prCTB can express p53, Ki67, glutamate decarboxylase (GAD65), heat shock protein 70 (HSP70), soluble CD40-ligand (sCD40L), B cell leukemia/lymphoma 2 related protein A1 (BCL2A1 or Bfl-1), and myeloid cell leukemia sequence 1 (Mcl-1). Functional outputs described include secretion and exosome compositions containing chemokines, cytokines, and growth factors.
Pharmaceutical compositions and therapeutic uses are directed to administering the isolated prCTB with a pharmaceutically acceptable excipient for treating diseases. The disclosures also include prCTB secretome and exosome compositions as compositions comprising chemokines, cytokines, and growth factors, and skin-cosmetic applications involving the prCTB secretome and exosomes.
Claims Coverage
The provided set contains three independent claims: a pharmaceutical composition, a genetically-engineered isolated prCTB, and a method for treating a disease. Across these independent claims, the coverage centers on a defined marker expression profile for prCTB with PD-1 absence, with additional emphasis on specified marker sets and an engineered option via genetic modification.
Pharmaceutical composition with PD-1-lacking marker-defined prCTB
A pharmaceutical composition that comprises an isolated precursory regulatory cytotrophoblast (prCTB) and a pharmaceutically acceptable excipient, wherein the prCTB expresses a specified first set of marker proteins and expresses a specified second set of marker proteins, and wherein the prCTB lacks expression of programmed cell death protein 1 (PD-1).
Genetically-engineered PD-1-lacking marker-defined prCTB
A genetically-engineered, isolated, precursory regulatory cytotrophoblast (prCTB), wherein the prCTB expresses specified marker proteins and further expresses specified additional marker proteins, and wherein the prCTB lacks expression of programmed cell death protein 1 (PD-1).
Therapeutic administration of PD-1-lacking marker-defined prCTB
A method for treating a disease comprising administering to a subject in need thereof an isolated precursory regulatory cytotrophoblast (prCTB), wherein the prCTB expresses a specified first set of marker proteins and expresses a specified second set of marker proteins, and wherein the prCTB lacks expression of programmed cell death protein 1 (PD-1).
All independent claims require an isolated prCTB having a defined expression profile for multiple markers and explicitly lacking PD-1 expression. The pharmaceutical and treatment claims further anchor the prCTB marker profile to the same two specified marker-group expressions, while the genetically-engineered claim additionally characterizes the prCTB as genetically engineered.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating a disease by administering an isolated precursory regulatory cytotrophoblast (prCTB) that lacks PD-1 expression and expresses specified marker proteins.
Treating cancer, including solid tumors, as further specified in dependent claims described in the provided claim context.
Use involving prCTB induction of apoptosis in a cancer cell as further specified in the provided dependent-claim context.
Skin-cosmetic applications involving prCTB secretome and exosome compositions.
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