US 11,667,900 B2
Compositions and methods for enhancing macrophage-mediated antibody guided cancer cell or tumor eradication
Yingxiao Wang, San Diego, CA (US); Shu Chien, La Jolla, CA (US); Lei Lei, San Diego, CA (US); Shaoying Lu, San Diego, CA (US); and Jie Sun, San Diego, CA (US)
Assigned to The Regents of the University of California, Oakland, CA (US)
Appl. No. 16/631,041
Filed by The Regents of the University of California, Oakland, CA (US)
PCT Filed Jul. 12, 2018, PCT No. PCT/US2018/041766
§ 371(c)(1), (2) Date Jan. 14, 2020,
PCT Pub. No. WO2019/014419, PCT Pub. Date Jan. 17, 2019.
Claims priority of provisional application 62/532,661, filed on Jul. 14, 2017.
Prior Publication US 2020/0140834 A1, May 7, 2020
Int. Cl. C12N 9/16 (2006.01); A61K 38/00 (2006.01); A61K 39/395 (2006.01); C07K 14/435 (2006.01)
CPC C12N 9/16 (2013.01) [A61K 39/39558 (2013.01); C07K 14/435 (2013.01); C12Y 301/03048 (2013.01); A61K 38/00 (2013.01); C07K 2319/03 (2013.01); C07K 2319/61 (2013.01)] 23 Claims
 
1. A Src homology region 2 domain-containing phosphatase-2 (Shp2)-actuating protein (iSNAP) (Shp2-iSNAP) chimeric protein comprising in either: amino terminal to carboxy terminal order, or carboxy terminal to amino terminal order, modules comprising:
(a) a bi-phosphorylatable peptide comprising a bisphosphoryl tyrosine-based activation (BTAM) motif,
(b) a Fluorescent Protein (FP) Förster Resonance Energy Transfer (FRET) (FP FRET) pair comprising an enhanced cyan fluorescent protein (ECFP) motif and a YPet fluorochrome,
(c) a truncated Shp2 domain consisting of an N-Src Homology 2 (N-SH2) domain and a C-Src Homology 2 (C-SH2) domain,
wherein an unphosphorylated Shp2 domain binds or quenches the PTP domain or the kinase domain; and,
(d) a phosphatase (PTP) domain or a kinase domain,
and when the bi-phosphorylatable peptide, when phosphorylated, binds the N-SH2 domain and the C-SH2 domain and liberates or unquenches or activates the PTP domain or the kinase domain, and unquenching or activating of the PTP domain or the kinase domain causes or results in the emission of a detectable signal by the YPet fluorochrome.