	US 12,466,868 B2
	Engineered proteins to enhance sensitivity of a cell to IL-2
Kenan Christopher Garcia, Menlo Park, CA (US); Sean Parker, Palo Alto, CA (US); Jonathan Sockolosky, San Francisco, CA (US); and Michael Hollander, Stanford, CA (US)
Assigned to The Board of Trustees of the Leland Stanford Junior University, Stanford, CA (US); and Park Institute for Cancer Immunotherapy, San Francisco, CA (US)
Filed by The Board of Trustees of the Leland Stanford Junior University, Stanford, CA (US); and Parker Institute for Cancer Immunotherapy, San Francisco, CA (US)
Filed on Sep. 1, 2023, as Appl. No. 18/460,452.
Application 18/460,452 is a division of application No. 16/769,535, granted, now 11,780,899, previously published as PCT/US2018/064086, filed on Dec. 5, 2018.
Claims priority of provisional application 62/595,316, filed on Dec. 6, 2017.
Prior Publication US 2024/0092855 A1, Mar. 21, 2024
Int. Cl. A61K 38/00 (2006.01); C07K 14/55 (2006.01); C07K 14/715 (2006.01)

CPC C07K 14/55 (2013.01) [C07K 14/7155 (2013.01); A61K 38/00 (2013.01); C07K 2319/00 (2013.01)]

9 Claims

1. A method of increasing the sensitivity of a human immune cell to IL-2, the method comprising engineering a cell by:

(i) introducing into the cell a polynucleotide encoding a non-signaling receptor that binds to IL-2 wherein the non-signaling receptor is a full-length CD25 polypeptide comprising a set of amino acid modifications selected from the group consisting of: (1) D4E; M25A, N27V, E29D, S39A, G40A, S41T, L42A, I118T, H120L, K153E; (2) M251, N27V, E29D, L42A, I118R, H120W, K153Q; (3) L2Q, M251, N27Y, L42A, I118R, H120W, K153Q; (4) L2Q, M25V, N27Y, L42A, I118R, H120W; and (5) M25L, N27V, L42A, I118N, H120M, K153G, numbering relative to SEQ ID NO:1, to generate an engineered cell; and

contacting the engineered cell with IL-2.