IP Library › Granted Patent US 12,258,381
Granted Patent B2
US 12,258,381 · App. 16/967,881 · Granted Mar 25, 2025

Activating chimeric receptors and uses thereof in natural killer cell immunotherapy

Inventors: See Voon Seow (Singapore, SG); Dario Campana (Singapore, SG)
Assignee: National University of Singapore
C07K14/70517A61K39/4613A61K39/4631A61K39/464402A61P35/00C07K14/7051C07K14/7056C07K14/70578C12N5/0646C12N15/113C12N15/62A61K2239/38A61K2239/50C07K2319/03C07K2319/33C12N2310/14C12N2310/531
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Quick Facts
Patent No.
US 12,258,381
App. No.
16/967,881
Granted
Mar 25, 2025
Kind
B2
Abstract

Current invention relates to a polynucleotide encoding activating chimeric receptors comprising engineered Natural Killer Group 2 member C (NKG2C) having enhanced affinity for HLA class I histocompatibility antigen alpha chain E (HLA-E)/peptide complex or an extracellular receptor domain of NKG2A coupled to an effector domain. It also relates to NK cells expressing such constructs and the use of these NK cells to induce cytotoxicity. It further exemplifies that the NK cells expressing polynucleotide encoding NKG2C (SIIS)/CD94/DAP12 or NKG2C/CD94/4-1 BB/CD3z showed enhanced NK cytotoxicity against cancer cells.

Claims (21)

1. A population of Natural Killer (NK) cells expressing a first chimeric receptor and a second chimeric receptor, wherein:

a) the first chimeric receptor comprises an extracellular receptor domain, wherein said extracellular receptor domain comprises an engineered Natural Killer Group 2 member C (NKG2C) variant that comprises the amino acid sequence of SEQ ID NO. 64; and

b) the second chimeric receptor comprises an extracellular receptor domain, wherein said extracellular receptor domain comprises an engineered variant of Natural Killer Group 2 member A (NKG2A),

wherein the engineered variant of NKG2A is coupled to an effector domain comprising a transmembrane region and an intracellular signaling domain,

wherein the engineered NKG2A variant consists of the amino acid sequence of SEQ ID NO. 66.

2. The population of NK cells of claim 1 , wherein NK cells of the population further express a chimeric CD94 receptor.

3. The population of NK cells of claim 2 , wherein the chimeric CD94 receptor comprises a fragment of CD94 coupled to a CD8a transmembrane domain and an effector domain comprising 4-1BB and CD3zeta, wherein the fragment of CD94 comprises the amino acid sequence of SEQ ID NO. 68.

4. The population of NK cells of claim 1 , wherein the effector domain comprises a CD8a transmembrane domain and the intracellular signaling domain comprises 4-1BB and CD3zeta.

5. The population of NK cells of claim 1 , wherein NK cells of the population further express a short hairpin RNA (shRNA) that specifically inhibits transcription or translation of native NKG2A.

6. The population of NK cells of claim 1 , wherein the population further expresses a chimeric CD94 receptor, wherein the chimeric CD94 receptor comprises an extracellular receptor domain, wherein said extracellular receptor domain comprises a CD94 fragment comprising the amino acid sequence of SEQ ID NO. 68.

7. The population of NK cells of claim 1 , wherein NK cells of the population further express a membrane-bound interleukin 15 (mbIL15).

8. The population of NK cells of claim 7 , wherein the mbIL15 comprises the amino acid sequence of SEQ ID NO. 17.

9. The population of NK cells of claim 7 , wherein the mbIL15 is encoded by the nucleic acid sequence of SEQ ID NO. 16.

10. The population of NK cells of claim 1 , wherein the second chimeric receptor is encoded by a nucleic acid sequence of SEQ ID NO. 61.

11. The population of NK cells of claim 1 , wherein the second chimeric receptor comprises the amino acid sequence of SEQ ID NO. 62.

12. The population of NK cells claim 1 , wherein the second chimeric receptor further comprises a hinge region.

13. The population of NK cells of claim 12 , wherein the hinge region is encoded by the nucleic acid sequence of SEQ ID NO. 5.

14. The population of NK cells of claim 1 , wherein NK cells of the population further express a chimeric receptor comprising: (a) an extracellular receptor domain, wherein said extracellular receptor domain binds native ligands of Natural Killer Group 2 member D (NKG2D); and (b) an effector domain comprising a transmembrane region and an intracellular signaling domain.

15. The population of NK cells of claim 1 , wherein the first chimeric receptor further comprises a transmembrane region that is a native NKG2C transmembrane region and an intracellular signaling domain that is a native NKG2C intracellular signaling domain.

16. The population of NK cells of claim 1 , wherein NK cells of the population further express DNAX-activating protein 12 (DAP12).

17. The population of NK cells of claim 2 , wherein NK cells of the population further express DNAX-activating protein 12 (DAP12).

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 10, 2020
From: SEOW, SEE VOON; CAMPANA, DARIO
To: NATIONAL UNIVERSITY OF SINGAPORE
Reel/Frame 053444/0692 →
Continuity (3)
Provisional Application 62736879 · Sep 26, 2018
Provisional Application 62628788 · Feb 9, 2018
Related Publication 20210046115A1 · Feb 18, 2021
References Cited (400)
US 4650764A · Temin et al. · 1987 [cited by applicant]
US 4690915A · Rosenberg · 1987 [cited by applicant]
US 4844893A · Honsik et al. · 1989 [cited by applicant]
US 4980289A · Temin et al. · 1990 [cited by applicant]
US 5124263A · Temin et al. · 1992 [cited by applicant]
US 5359046A · Capon · 1994 [cited by applicant]
US 5399346A · Anderson et al. · 1995 [cited by applicant]
US 5653977A · Saleh · 1997 [cited by applicant]
US 5674704A · Goodwin et al. · 1997 [cited by applicant]
US 5686281A · Roberts · 1997 [cited by applicant]
US 5712149A · Roberts · 1998 [cited by applicant]
US 6103521A · Capon et al. · 2000 [cited by applicant]
US 6303121B1 · Kwon · 2001 [cited by applicant]
US 6319494B1 · Capon et al. · 2001 [cited by applicant]
US 6355476B1 · Kwon et al. · 2002 [cited by applicant]
US 6361998B1 · Bell et al. · 2002 [cited by applicant]
US 6410319B1 · Raubitschek et al. · 2002 [cited by applicant]
US 6797514B2 · Berenson et al. · 2004 [cited by applicant]
US 7052906B1 · Lawson et al. · 2006 [cited by applicant]
US 7070995B2 · Jensen · 2006 [cited by applicant]
US 7435596B2 · Campana et al. · 2008 [cited by applicant]
US 7446179B2 · Jensen et al. · 2008 [cited by applicant]
US 7446190B2 · Sadelain et al. · 2008 [cited by applicant]
US 7763243B2 · Lum et al. · 2010 [cited by applicant]
US 7932055B2 · Spee et al. · 2011 [cited by applicant]
US 7994298B2 · Zhang et al. · 2011 [cited by applicant]
US 8026097B2 · Campana et al. · 2011 [cited by applicant]
US 8399645B2 · Campana et al. · 2013 [cited by applicant]
US 9487800B2 · Schonfeld et al. · 2016 [cited by applicant]
US 9511092B2 · Campana et al. · 2016 [cited by applicant]
US 9605049B2 · Campana et al. · 2017 [cited by applicant]
US 9834590B2 · Campana et al. · 2017 [cited by applicant]
US 9856322B2 · Campana et al. · 2018 [cited by applicant]
US 10428305B2 · Campana et al. · 2019 [cited by applicant]
US 10538739B2 · Campana et al. · 2020 [cited by applicant]
US 10736920B2 · Yu et al. · 2020 [cited by applicant]
US 10774309B2 · Campana et al. · 2020 [cited by applicant]
US 10774311B2 · Campana et al. · 2020 [cited by applicant]
US 10801012B2 · Campana et al. · 2020 [cited by applicant]
US 10829737B2 · Campana et al. · 2020 [cited by applicant]
US 10836999B2 · Campana et al. · 2020 [cited by applicant]
US 11141436B2 · Trager et al. · 2021 [cited by applicant]
US 11154575B2 · Trager et al. · 2021 [cited by applicant]
US 11253547B2 · Trager et al. · 2022 [cited by applicant]
US 11365236B2 · Leong et al. · 2022 [cited by applicant]
US 11560548B2 · Campana et al. · 2023 [cited by applicant]
US 11673937B2 · Campana et al. · 2023 [cited by applicant]
US 11873512B2 · Campana et al. · 2024 [cited by applicant]
US 11896616B2 · Kamiya et al. · 2024 [cited by applicant]
US 20020018783A1 · Sadelain et al. · 2002 [cited by applicant]
US 20030129649A1 · Kobilka · 2003 [cited by examiner]
US 20030147869A1 · Riley · 2003 [cited by applicant]
US 20030215427A1 · Jensen · 2003 [cited by applicant]
US 20040038886A1 · Finney et al. · 2004 [cited by applicant]
US 20040043401A1 · Sadelain et al. · 2004 [cited by applicant]
US 20040126363A1 · Jensen et al. · 2004 [cited by applicant]
US 20050042208A1 · Sagawa et al. · 2005 [cited by applicant]
US 20050048549A1 · Cao et al. · 2005 [cited by applicant]
US 20050113564A1 · Campana et al. · 2005 [cited by applicant]
US 20060093605A1 · Campana et al. · 2006 [cited by applicant]
US 20060247191A1 · Finney et al. · 2006 [cited by applicant]
US 20070160578A1 · Waldmann et al. · 2007 [cited by applicant]
US 20070166327A1 · Cooper et al. · 2007 [cited by applicant]
US 20080177047A1 · Fujita-Yamaguchi · 2008 [cited by applicant]
US 20080247990A1 · Campbell · 2008 [cited by applicant]
US 20080299137A1 · Svendsen · 2008 [cited by examiner]
US 20090281035A1 · Spee · 2009 [cited by examiner]
US 20100029749A1 · Zhang · 2010 [cited by examiner]
US 20120015434A1 · Campana et al. · 2012 [cited by applicant]
US 20120148552A1 · Jensen · 2012 [cited by applicant]
US 20120282256A1 · Campana et al. · 2012 [cited by applicant]
US 20120321666A1 · Copper et al. · 2012 [cited by applicant]
US 20130072401A1 · Ye · 2013 [cited by examiner]
US 20130266551A1 · Campana et al. · 2013 [cited by applicant]
US 20130280221A1 · Schonfeld et al. · 2013 [cited by applicant]
US 20130288368A1 · June et al. · 2013 [cited by applicant]
US 20140023626A1 · Peled et al. · 2014 [cited by applicant]
US 20140271635A1 · Brogdon et al. · 2014 [cited by applicant]
US 20140286973A1 · Powell, Jr. · 2014 [cited by applicant]
US 20140302608A1 · Dominici et al. · 2014 [cited by applicant]
US 20150139943A1 · Campana et al. · 2015 [cited by applicant]
US 20150190471A1 · Copik et al. · 2015 [cited by applicant]
US 20150218649A1 · Saenger et al. · 2015 [cited by applicant]
US 20160000828A1 · Campana et al. · 2016 [cited by applicant]
US 20160362472A1 · Bitter et al. · 2016 [cited by applicant]
US 20160152723A1 · Chen et al. · 2016 [cited by applicant]
US 20160158285A1 · Cooper et al. · 2016 [cited by applicant]
US 20170044227A1 · Schonfeld · 2017 [cited by applicant]
US 20170073423A1 · Juillerat et al. · 2017 [cited by applicant]
US 20170073638A1 · Campana · 2017 [cited by examiner]
US 20170129967A1 · Wels et al. · 2017 [cited by applicant]
US 20170283482A1 · Campana et al. · 2017 [cited by applicant]
US 20170355957A1 · Biondi et al. · 2017 [cited by applicant]
US 20170368098A1 · Chen et al. · 2017 [cited by applicant]
US 20180002397A1 · Shah et al. · 2018 [cited by applicant]
US 20180044391A1 · Gundram et al. · 2018 [cited by applicant]
US 20180044417A1 · Puléet al. · 2018 [cited by applicant]
US 20180046571A1 · Magill et al. · 2018 [cited by applicant]
US 20180086831A1 · Pule et al. · 2018 [cited by applicant]
US 20180104278A1 · Zhang et al. · 2018 [cited by applicant]
US 20180117146A1 · Yu et al. · 2018 [cited by applicant]
US 20180134765A1 · Landgraf et al. · 2018 [cited by applicant]
US 20180371052A1 · Ma et al. · 2018 [cited by applicant]
US 20190038733A1 · Campana et al. · 2019 [cited by applicant]
US 20190046571A1 · Campana et al. · 2019 [cited by applicant]
US 20190062430A1 · Wu et al. · 2019 [cited by applicant]
US 20190290693A1 · Qi et al. · 2019 [cited by applicant]
US 20190336533A1 · Hwang et al. · 2019 [cited by applicant]
US 20190376037A1 · Campana et al. · 2019 [cited by applicant]
US 20200016208A1 · Kamiya et al. · 2020 [cited by applicant]
US 20200116208A1 · Kamiya et al. · 2020 [cited by applicant]
US 20200131244A1 · Leong et al. · 2020 [cited by applicant]
US 20200255803A1 · Zhang et al. · 2020 [cited by applicant]
US 20200340995A1 · Campana et al. · 2020 [cited by applicant]
US 20200407686A1 · Campana et al. · 2020 [cited by applicant]
US 20210009951A1 · Hu et al. · 2021 [cited by applicant]
US 20210017271A1 · Tan et al. · 2021 [cited by applicant]
US 20210054409A1 · Zhu et al. · 2021 [cited by applicant]
US 20210324388A1 · Vinanica et al. · 2021 [cited by applicant]
US 20210338727A1 · Trager et al. · 2021 [cited by applicant]
US 20210363218A1 · Fan · 2021 [cited by examiner]
US 20220002424A1 · Trager et al. · 2022 [cited by applicant]
US 20220047635A1 · Liu et al. · 2022 [cited by applicant]
US 20220233590A1 · Trager et al. · 2022 [cited by applicant]
US 20220233593A1 · Trager et al. · 2022 [cited by applicant]
US 20220281971A1 · Shimasaki et al. · 2022 [cited by applicant]
US 20220411754A1 · Trager et al. · 2022 [cited by applicant]
US 20230002471A1 · Leong et al. · 2023 [cited by applicant]
US 20230028399A1 · Rajangam et al. · 2023 [cited by applicant]
US 20230220343A1 · Campana et al. · 2023 [cited by applicant]
US 20230265390A1 · Trager et al. · 2023 [cited by applicant]
US 20230390392A1 · Trager et al. · 2023 [cited by applicant]
CN 101684456A · 2010 [cited by applicant]
CN 103113470A · 2013 [cited by applicant]
CN 105838677A · 2016 [cited by applicant]
CN 105985931A · 2016 [cited by applicant]
CN 107109363A · 2017 [cited by applicant]
CN 107636015A · 2018 [cited by applicant]
CN 107827990A · 2018 [cited by applicant]
CN 108840930A · 2018 [cited by applicant]
EP 0952213A2 · 1999 [cited by applicant]
EP 0830599B1 · 2000 [cited by applicant]
EP 1231262A1 · 2002 [cited by applicant]
EP 1306427A1 · 2003 [cited by applicant]
EP 1053301B1 · 2004 [cited by applicant]
EP 1820017 · 2006 [cited by applicant]
EP 1233058B1 · 2006 [cited by applicant]
EP 1036327B1 · 2009 [cited by applicant]
EP 2411507 · 2010 [cited by applicant]
EP 2493485 · 2011 [cited by applicant]
EP 2493486 · 2011 [cited by applicant]
EP 2593542 · 2012 [cited by applicant]
EP 2141997B1 · 2012 [cited by applicant]
EP 2614151 · 2012 [cited by applicant]
EP 2756521 · 2013 [cited by applicant]
EP 2866834 · 2014 [cited by applicant]
EP 2903637 · 2014 [cited by applicant]
EP 2904106 · 2014 [cited by applicant]
EP 2948544 · 2014 [cited by applicant]
EP 2956175 · 2014 [cited by applicant]
EP 2961831 · 2014 [cited by applicant]
EP 2964753 · 2014 [cited by applicant]
EP 2970426 · 2014 [cited by applicant]
EP 2968601 · 2014 [cited by applicant]
EP 2986636 · 2014 [cited by applicant]
EP 2537416B1 · 2014 [cited by applicant]
EP 3008173 · 2014 [cited by applicant]
EP 2856876A1 · 2015 [cited by applicant]
EP 3057986 · 2015 [cited by applicant]
EP 3063175 · 2015 [cited by applicant]
EP 3071221 · 2015 [cited by applicant]
EP 3071222 · 2015 [cited by applicant]
EP 3071223 · 2015 [cited by applicant]
EP 3083671 · 2015 [cited by applicant]
EP 3083691 · 2015 [cited by applicant]
EP 3094653 · 2015 [cited by applicant]
EP 3105318 · 2015 [cited by applicant]
EP 3105335 · 2015 [cited by applicant]
EP 2968492 · 2015 [cited by applicant]
EP 3119425 · 2015 [cited by applicant]
EP 3126380 · 2015 [cited by applicant]
EP 3134432 · 2015 [cited by applicant]
EP 3180359 · 2016 [cited by applicant]
EP 3189132 · 2016 [cited by applicant]
EP 3012268A1 · 2016 [cited by applicant]
EP 2614077B1 · 2016 [cited by applicant]
EP 3115373A1 · 2017 [cited by applicant]
EP 3567049A2 · 2019 [cited by applicant]
EP 3690033A1 · 2020 [cited by applicant]
JP 2017112982A · 2017 [cited by applicant]
WO WO9217198A1 · 1992 [cited by applicant]
WO WO95007358A1 · 1995 [cited by applicant]
WO WO96023814A1 · 1996 [cited by applicant]
WO WO96024671A1 · 1996 [cited by applicant]
WO WO9641163A1 · 1996 [cited by applicant]
WO WO97023613A2 · 1997 [cited by applicant]
WO WO98026061A2 · 1998 [cited by applicant]
WO WO99000494A2 · 1999 [cited by applicant]
WO WO9906557A2 · 1999 [cited by applicant]
WO WO9938954A1 · 1999 [cited by applicant]
WO WO99057268A1 · 1999 [cited by applicant]
WO WO2000014257A1 · 2000 [cited by applicant]
WO WO0023573A2 · 2000 [cited by applicant]
WO WO200129191A1 · 2001 [cited by applicant]
WO WO200138494A1 · 2001 [cited by applicant]
WO WO200210350A1 · 2002 [cited by applicant]
WO WO2002033101A1 · 2002 [cited by applicant]
WO WO02077029A2 · 2002 [cited by applicant]
WO WO2003089616A2 · 2003 [cited by applicant]
WO WO2004027036A2 · 2004 [cited by applicant]
WO WO2004039840A1 · 2004 [cited by applicant]
WO 2005000890A1 · 2005 [cited by applicant]
WO WO2005044996A2 · 2005 [cited by applicant]
WO WO2005118788A2 · 2005 [cited by applicant]
WO WO2006036445A2 · 2006 [cited by applicant]
WO WO2006052534A2 · 2006 [cited by applicant]
WO WO2006061626A2 · 2006 [cited by applicant]
WO 2006119115A2 · 2006 [cited by applicant]
WO WO2007046006A2 · 2007 [cited by applicant]
WO WO2008121420A1 · 2008 [cited by applicant]
WO WO2009117566A1 · 2009 [cited by applicant]
WO WO2010071836A1 · 2010 [cited by applicant]
WO WO2010110734A1 · 2010 [cited by applicant]
WO WO2011020047A1 · 2011 [cited by applicant]
WO WO2011053321A1 · 2011 [cited by applicant]
WO WO2011053322A1 · 2011 [cited by applicant]
WO WO2011069019A2 · 2011 [cited by applicant]
WO WO2011080740A1 · 2011 [cited by applicant]
WO WO2011150976A1 · 2011 [cited by applicant]
WO WO2012009422A1 · 2012 [cited by applicant]
WO WO2012031744A1 · 2012 [cited by applicant]
WO WO2012040323A2 · 2012 [cited by applicant]
WO WO2012071411A2 · 2012 [cited by applicant]
WO WO2012079000A1 · 2012 [cited by applicant]
WO WO2012136231A1 · 2012 [cited by applicant]
WO 2013043196A1 · 2013 [cited by applicant]
WO WO2013040371A2 · 2013 [cited by applicant]
WO WO2013040557A2 · 2013 [cited by applicant]
WO WO2013123720A2 · 2013 [cited by applicant]
WO WO2013123726A1 · 2013 [cited by applicant]
WO WO2014005072A1 · 2014 [cited by applicant]
WO WO2014011993A2 · 2014 [cited by applicant]
WO WO2014055413A2 · 2014 [cited by applicant]
WO WO2014055442A2 · 2014 [cited by applicant]
WO WO2014055657A1 · 2014 [cited by applicant]
WO WO2014055668A1 · 2014 [cited by applicant]
WO WO2014099671A1 · 2014 [cited by applicant]
WO WO2014117121A1 · 2014 [cited by applicant]
WO WO2014127261A1 · 2014 [cited by applicant]
WO WO2014134165A1 · 2014 [cited by applicant]
WO WO2014138704A1 · 2014 [cited by applicant]
WO WO2014145252A2 · 2014 [cited by applicant]
WO WO2014164554A1 · 2014 [cited by applicant]
WO WO2014172584A1 · 2014 [cited by applicant]
WO WO2014186469A2 · 2014 [cited by applicant]
WO WO2014201021A2 · 2014 [cited by applicant]
WO WO2015058018A1 · 2015 [cited by applicant]
WO WO2015066551A2 · 2015 [cited by applicant]
WO WO2015075468A1 · 2015 [cited by applicant]
WO WO2015075469A1 · 2015 [cited by applicant]
WO WO2015075470A1 · 2015 [cited by applicant]
WO WO2015092024A2 · 2015 [cited by applicant]
WO WO2015095895A1 · 2015 [cited by applicant]
WO WO2015105522A1 · 2015 [cited by applicant]
WO WO2015120421A1 · 2015 [cited by applicant]
WO WO2015123642A1 · 2015 [cited by applicant]
WO WO2015142314A1 · 2015 [cited by applicant]
WO WO2015142661A1 · 2015 [cited by applicant]
WO WO2015150771A1 · 2015 [cited by applicant]
WO WO2015154012A1 · 2015 [cited by applicant]
WO WO2015154012A8 · 2015 [cited by applicant]
WO WO2015164759A2 · 2015 [cited by applicant]
WO WO2015174928A1 · 2015 [cited by applicant]
WO 2015188119A1 · 2015 [cited by applicant]
WO WO2015193411A1 · 2015 [cited by applicant]
WO 2016014576A1 · 2016 [cited by applicant]
WO WO2016011210A2 · 2016 [cited by applicant]
WO WO2016030691A1 · 2016 [cited by applicant]
WO WO2016033331A1 · 2016 [cited by applicant]
WO WO2016040441A1 · 2016 [cited by applicant]
WO WO2016042041A1 · 2016 [cited by applicant]
WO WO2016042461A1 · 2016 [cited by applicant]
WO WO2016061574A1 · 2016 [cited by applicant]
WO 2016073755A9 · 2016 [cited by applicant]
WO WO2016069607A1 · 2016 [cited by applicant]
WO WO2016073602A2 · 2016 [cited by applicant]
WO WO2016073629A1 · 2016 [cited by applicant]
WO WO2016073755A2 · 2016 [cited by applicant]
WO WO2016075612A1 · 2016 [cited by applicant]
WO WO2016100985A2 · 2016 [cited by applicant]
WO 2016118857A1 · 2016 [cited by applicant]
WO WO2016109661A1 · 2016 [cited by applicant]
WO WO2016109668A1 · 2016 [cited by applicant]
WO WO2016115482A1 · 2016 [cited by applicant]
WO 2016126213A1 · 2016 [cited by applicant]
WO 2017040324A1 · 2016 [cited by applicant]
WO WO2016123122A1 · 2016 [cited by applicant]
WO WO2016123333A1 · 2016 [cited by applicant]
WO WO2016124765A1 · 2016 [cited by applicant]
WO WO2016124930A1 · 2016 [cited by applicant]
WO WO2016126608A1 · 2016 [cited by applicant]
WO 2016139487A1 · 2016 [cited by applicant]
WO WO2016141357A1 · 2016 [cited by applicant]
WO WO2016142314A1 · 2016 [cited by applicant]
WO WO2016149254A1 · 2016 [cited by applicant]
WO WO2016151315A1 · 2016 [cited by applicant]
WO WO2016154055A1 · 2016 [cited by applicant]
WO WO2016154585A1 · 2016 [cited by applicant]
WO WO2016172537A1 · 2016 [cited by applicant]
WO WO2016172583A1 · 2016 [cited by applicant]
WO WO2016174405A1 · 2016 [cited by applicant]
WO WO2016174406A1 · 2016 [cited by applicant]
WO WO2016174407A1 · 2016 [cited by applicant]
WO WO2016174408A1 · 2016 [cited by applicant]
WO WO2016174409A1 · 2016 [cited by applicant]
WO WO2016174461A1 · 2016 [cited by applicant]
WO WO2016174652A1 · 2016 [cited by applicant]
WO WO2016179684A1 · 2016 [cited by applicant]
WO WO2016191587A1 · 2016 [cited by applicant]
WO WO2016191755A1 · 2016 [cited by applicant]
WO WO2016196388A1 · 2016 [cited by applicant]
WO WO2016197108A1 · 2016 [cited by applicant]
WO WO2016201304A1 · 2016 [cited by applicant]
WO WO2016210293A1 · 2016 [cited by applicant]
WO WO2017004150A1 · 2017 [cited by applicant]
WO WO2017011804A1 · 2017 [cited by applicant]
WO WO2017021701A1 · 2017 [cited by applicant]
WO WO2017023859A1 · 2017 [cited by applicant]
WO WO2017024131A1 · 2017 [cited by applicant]
WO WO2017027325A1 · 2017 [cited by applicant]
WO WO2017029511A1 · 2017 [cited by applicant]
WO WO2017032777A1 · 2017 [cited by applicant]
WO WO2017034615A1 · 2017 [cited by applicant]
WO WO2017037083A1 · 2017 [cited by applicant]
WO WO2017058752A1 · 2017 [cited by applicant]
WO WO2017058753A1 · 2017 [cited by applicant]
WO WO2017079694A2 · 2017 [cited by applicant]
WO WO2017079705A1 · 2017 [cited by applicant]
WO WO2017079881A1 · 2017 [cited by applicant]
WO WO2017096329A1 · 2017 [cited by applicant]
WO WO2017127729A1 · 2017 [cited by applicant]
WO 2017172981A2 · 2017 [cited by applicant]
WO 2017186928A1 · 2017 [cited by applicant]
WO 2017222593A1 · 2017 [cited by applicant]
WO WO2018022646A1 · 2018 [cited by applicant]
WO 2018057915A1 · 2018 [cited by applicant]
WO 2018106732A1 · 2018 [cited by applicant]
WO WO2018103503A1 · 2018 [cited by applicant]
WO 2018124766A2 · 2018 [cited by applicant]
WO WO2018182511A1 · 2018 [cited by applicant]
WO WO2018183385A1 · 2018 [cited by applicant]
WO 2019028051A1 · 2019 [cited by applicant]
WO WO2019062817A1 · 2019 [cited by applicant]
WO WO2019077037A1 · 2019 [cited by applicant]
WO 2019091478A1 · 2019 [cited by applicant]
WO 2019112899A2 · 2019 [cited by applicant]
WO 2019129220A1 · 2019 [cited by applicant]
WO WO2019129002A1 · 2019 [cited by applicant]
WO WO2019155286A2 · 2019 [cited by applicant]
WO WO2019155288A1 · 2019 [cited by applicant]
WO 2019169290A1 · 2019 [cited by applicant]
WO 2019199689A1 · 2019 [cited by applicant]
WO WO2019193476A1 · 2019 [cited by applicant]
WO WO2020044239A1 · 2020 [cited by applicant]
WO WO2020083282A1 · 2020 [cited by applicant]
WO WO2021009694A1 · 2021 [cited by applicant]
Kaiser BK, Pizarro JC, Kerns J, Strong RK. Structural basis for NKG2A/CD94 recognition of HLA-E. Proc Natl Acad Sci U S A. May 6, 2008; 105(18):6696-701. doi: 10.1073/pnas.0802736105. (Year: 2008). [cited by examiner]
Qin L, Lai Y, Zhao R, Wei X, Weng J, Lai P, Li B, Lin S, Wang S, Wu Q, Liang Q, Li Y, Zhang X, Wu Y, Liu P, Yao Y, Pei D, Du X, Li P. Incorporation of a hinge domain improves the expansion of chimeric antigen receptor T… [cited by examiner]
Figueiredo C, Seltsam A, Blasczyk R. Permanent silencing of NKG2A expression for cell-based therapeutics. J Mol Med (Berl). Feb. 2009;87(2):199-210. (Year: 2009). [cited by examiner]
Call ME, Wucherpfennig KW, Chou JJ. The structural basis for intramembrane assembly of an activating immunoreceptor complex. Nat Immunol. Nov. 2010;11(11):1023-9. (Year: 2010). [cited by examiner]
Lanier LL. DAP10- and DAP12-associated receptors in innate immunity. Immunol Rev. Jan. 2009;227(1):150-60. doi: 10.1111/j. 1600-065X.2008.00720.x. PMID: 19120482; PMCID: PMC2794881. (Year: 2009). [cited by examiner]
UniProt P26717 NKG2C_HUMAN. Integrated into UniProtKB/Swiss-Prot Aug. 1, 1992. https://www.uniprot.org/uniprotkb/P26717/entry. Accessed Jul. 17, 2024 (Year: 1992). [cited by examiner]
Caratelli et al., “FCy Chimeric Receptor-Engineered T Cells: Methodology, Advantages, Limitations, and Clinical Relevance,” Front lmmunol., vol. 8, Article 457 , 8 pages (Apr. 27, 2017). [cited by applicant]
Hombach, A.A., et al., “Costimulation by chimeric antigen receptors revisited: the T cell antitumor response benefits from combined CD28-OX40 signalling”, Int. J. Cancer, 129, 2935-2944 (2011). [cited by applicant]
Hurton, L.V. et al., “Tethered IL-15 augments antitumor activity and promotes a stem-cell memory subset in tumor-specific T cells,” PCNAS, USA, 113(48): E7788-E7797 (Nov. 2016). [cited by applicant]
Kober, J., et al. “The capacity of the TNF family members 4-1BBL, OX40L, CD70, GITRL, CD30L and Light to costimulate human T cells,” Eur J Immuno, vol. 38, No. 10, pp. 2678-2688 (Oct. 28, 2008). [cited by applicant]
NCIthesaurus, Bicistronic chimeric antigen reeptor vector, retrieved online from: https://ncit.nci.nih.gov/ncitbrowser/pages/home.jsf.jsessionid=12B0F7AF71E9A4035C38B5E4F6C055B0, retrieved on: Jan. 21, 2021. [cited by applicant]
Abakushina, E.V., “Immunotherapy With Natural Killer Cells In The Treatment Of Cancer,” Russian Journal of Immunology, vol. 10, No. 2, pp. 131-142 (2016) (Abstract only). [cited by applicant]
Pakula, A.A. et al., “Genetic analysis of protein stability and function,” Annual Review of Genetics, V. 23, N. 1, p. 289-310, c. 305-306 (1989). [cited by applicant]
Ye et al. “Effects of target cell overexpression of IL-15, 4-1 BBL and IL-18 1-102 combine with IL-2 on NK cell activation and cytotoxicity during ex vivo expansion” Chin J Cancer Biother, Oct. 31, 2014, vol. 21, No. 5,… [cited by applicant]
Gacerez, A, et al., “How Chimeric Antigen Receptor Design Affects Adoptive T Cell Therapy,” Journal of Cellular Physiology, vol. 231, No. 12, pp. 2590-2598; Jun. 2, 2016. [cited by applicant]
Sadelain, M. et al., “The Basic Principles of Chimeric Antigen Receptor Design,” Cancer Discovery, vol. 3, No. 4, pp. 388-398 (Apr. 1, 2013). [cited by applicant]
Wang, W., “NK cell-mediated antibody-dependent cellular cytotoxicity in cancer immunotherapy,” Frontiers in Immunology, 2015, 6, 368. [cited by applicant]
Ren, P.-P. et al., Anti-EGFRvIII Chimeric Antigen Receptor-Modified T Cells for Adoptive Cell Therapy of Glioblastoma, Current Pharmaceutical Design, 23(14), 2113-2116 (2017). [cited by applicant]
Morgan, R.A. et. al., Recognition of Glioma Stem Cells by Genetically Modified T Cells Targeting EGFRvIII and Development of Adoptive Cell Therapy for Glioma, Human Gene Therapy, 23(10), 1043-1053 (2012). [cited by applicant]
Dalal, A.-R. et al., Third-Generation Human Epidermal Growth Factor Receptor 2 Chimeric Antigen Receptor Expression on Human T Cells Improves with Two-Signal Activation, Human Gene Therapy, 845-852 (2018) (Abstract). [cited by applicant]
Choi, B. D. et al., Chimeric antigen receptor T-cell immunotherapy for glioblastoma: practical insights for neurosurgeons, Neurosurg Focus, 44(6):E13, 1-6 (2018). [cited by applicant]
Mirzaei, H.R., et al., “Construction and functional characterization of a fully human anti-CD19 chimeric antigen receptor (huCAR)-expressing primary human T cells,” J Cell Physiol. Jun. 2019; 234(6):9207-9215. doi: 10.1… [cited by applicant]
Chen, F., “Construction of Anti-CD20 Single-Chain Antibody-CD28-CD137-TCR Recombinant Genetic Modified T Cells and its Treatment Effect on B Cell Lymphoma,” Med Sci Monit 2015; 21:2110-2115 (Jul. 21, 2015). [cited by applicant]
Kohrt, H.E., “Immunomodulation of NK Cells through 4-1BB (CD137) to Improve the Anti-Lymphoma Activity of Rituximab: Antibody-Based Anti-Lymphoma Snergy,” Blood, 2010, 116(21), 422 (Abstract). [cited by applicant]
Robak, T., New Anti-CD20 Monoclonal Antibodies for the Treatment of B-Cell Lymphoid Malignancies, BioDrugs 25, 13-25 (2011) (Abstract). [cited by applicant]
Kochenderfer, J.N., “Eradication of B-lineage and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19,” Blood, 2010, 116(20), 4099-4102. [cited by applicant]
Schmohl J.U., et al., Tetraspecific scFv construct provides NK cell mediated ADCC and self-sustaining stimuli via Insertion of IL-15 as a cross-linker. Oncotarget. 2016; 7: 73830-73844. [cited by applicant]
Vinanica, N., et al., “Specific stimulation of T lymphocytes with erythropoietin for adoptive immunotherapy”, Blood, 135(9): 668-679 (Feb. 27, 2020). [cited by applicant]
Zuther, “Generation of the Plasmid pMT/BiP SCA431scFv-Fc-IL 15 (#1118),” Chapter 4.1.8 of An Anti-CD30 Immunocytokine with Combined IL-2 and IL-12 Domains Enhances Anti-Tumor Immunity, p. 70 (Oct. 1, 2009). [cited by applicant]
Imamura, M. et al., “Autonomous growth and increased cytotoxicity of natural killer cells expressing membrane-bound Interleukin-15,” Blood, 124(7): 1081-1088 (2014). [cited by applicant]
Suarez, et al., “Chimeric Antigen Receptor T Cells Secreting Anti-PD-L1 Antibodies More Effectively Regress Renal Cell Carcinoma in a Humanized Mouse Model,” Oncotarget, vol. 7, No. 23, Apr. 29, 2016. [cited by applicant]
Li, et al., “Therapeutically Targeting Glypican-2 via Single-Domain Antibody-Based Chimeric Antigen Receptors and Immunotoxins in Neuroblasoma,” PNAS, pp. E6623-E6631 (Jul. 24, 2017). [cited by applicant]
Abken et al., “Chimeric T-cell receptors: highly specific tools to target cytotoxic T-lymphocytes to tumour cells,” Cancer Treat Rev., 23(2): 97-112, Mar. 1997. [cited by applicant]
Abken, H., et al., “Tuning tumor-specific T-cell activation: a matter of costimulation?” Trends in Immunol. 23: 240-245 (2002). [cited by applicant]
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