US 11,913,959 B2
Methods of treating and prognosing nonhematopoietic malignant tumors
Larry Norton, New York, NY (US); Ross Levine, New York, NY (US); Maria Kleppe, New York, NY (US); and Elizabeth Comen, New York, NY (US)
Assigned to Memorial Sloan Kettering Cancer Center, New York, NY (US)
Filed by Memorial Sloan Kettering Cancer Center, New York, NY (US)
Filed on Mar. 19, 2021, as Appl. No. 17/207,412.
Application 17/207,412 is a continuation of application No. 15/533,911, granted, now 10,962,543, previously published as PCT/US2015/064016, filed on Dec. 4, 2015.
Claims priority of provisional application 62/089,148, filed on Dec. 8, 2014.
Prior Publication US 2021/0263035 A1, Aug. 26, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. C12Q 1/6886 (2018.01); G01N 33/574 (2006.01); C07K 16/28 (2006.01); A61K 31/7068 (2006.01); A61K 31/7052 (2006.01); A61K 31/52 (2006.01); A61K 31/573 (2006.01); A61K 31/704 (2006.01); A61K 31/7048 (2006.01); A61K 31/506 (2006.01); A61K 38/17 (2006.01); A61K 39/395 (2006.01); A61K 45/06 (2006.01); A61K 31/00 (2006.01)
CPC G01N 33/57484 (2013.01) [A61K 31/506 (2013.01); A61K 31/52 (2013.01); A61K 31/573 (2013.01); A61K 31/704 (2013.01); A61K 31/7048 (2013.01); A61K 31/7052 (2013.01); A61K 31/7068 (2013.01); A61K 38/177 (2013.01); A61K 39/3955 (2013.01); A61K 45/06 (2013.01); C12Q 1/6886 (2013.01); G01N 33/57496 (2013.01); A61K 31/00 (2013.01); C12Q 2600/136 (2013.01); C12Q 2600/158 (2013.01); G01N 2800/52 (2013.01); G01N 2800/56 (2013.01); G01N 2800/7028 (2013.01)] 22 Claims
 
1. A method of treating mutant tumor-infiltrating leukocytes comprising:
determining that a patient having a nonhematopoietic malignant tumor comprising a breast tumor has one or more somatic gene mutations present in tumor-infiltrating leukocytes of the breast tumor, wherein the one or more somatic gene mutations are present in one or more genes selected from the group consisting of KDM5C, CDK8, MPL, ARID1A, FLT3, FGFR1, JAK1, GLI1, EZH2, EP300, BCOR, NF1, SMARCB1, EPHA10, IRF4, INSR, EPHA2, SMO, DUSP27, NOTCH2, HNF1A, MYO18A, MET, RPTOR, ATP10A, PTCH1, BRCA1, NCOR2, PASD1, NEB, MUC4, POU2F2, HLA-A, ALK, TET2, HLA-B, FGFR4, GATA2, FLT1, ATM, ITK, FREM2, INPP4B, CSF1R, PIGN, SOX17, MLL4, TTC28, TNFSF9, TRRAP, DNMT3A, TP53, IDH2, EPHA7, WT1, PNRC1, EGFR, ETV6, SMARCA4, MLL2, MAP3K1, ALOX12B, ARID2, EPHA8, ERBB2, EPHA4, PBRM1, BCL6, HDAC2, EPHA7, MEL, CYLD, CEBPA, JAK3, ASXL1, KIT, MEF2B, and ERG; are in a coding region, and result in an amino acid substitution or a premature stop codon; and are not identified in neoplastic cells of the breast tumor itself; and
administering to the patient determined to have the one or more somatic gene mutations present in the tumor-infiltrating leukocytes of the breast tumor an agent that preferentially kills or inhibits proliferation or activity of leukocytes relative to nonhematopoietic cells, wherein the agent is known or indicated to treat leukemia and comprises a leukocyte-specific antibody.