Enhanced chimeric antigen receptor cells in hypoxic tumor microenvironment
AssigneesInnovative Cellular Therapeutics Holdings, Ltd., Innovative Cellular Therapeutics, Inc.
InventorsXiaogang Shen, Xudong Tang, Chengfei Pu, Lei Xiao, Le Tian
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Abstract
Embodiments of the present disclosure relate to compositions and methods of enhancing lymphocytes' ability to treat cancer patients. Embodiments relate to a polynucleotide comprising a nucleic acid encoding a chimeric antigen receptor (CAR), a nucleic acid encoding an Oxygen-Dependent Degradation domain (ODD), and a nucleic acid encoding one or multiple sequences of Hypoxia-Response Element (HRE).
Claims19
A method of maintaining a population of T cells expressing a chimeric antigen receptor (CAR) under hypoxic conditions, the method comprising:
- introducing a polynucleotide comprising a nucleic acid encoding an Oxygen-Dependent Degradation domain (ODD) comprising SEQ ID NO:
- 17 and a nucleic acid comprising one or more sequences of Hypoxia-Response Element (HRE) and a nucleic acid encoding the CAR into a population of T cells;
- and
- exposing the population of T cells to a hypoxic condition, wherein maintenance of the population of T cells is higher than that of a population of T cells without the nucleic acid encoding the ODD and the nucleic acid comprising one or more sequences of HRE.
Dependencies are inferred from the claim text.