US 12,111,319 B2
Articles and methods directed to personalized therapy of cancer
Alexey Vyacheslavovich Stepanov, Moscow (RU); Dmitry Dmitrievich Genkin, St. Petersburg (RU); Alexander Gabibovich Gabibov, Moscow (RU); Richard A. Lerner, La Jolla, CA (US); Alexey Anatolievich Belogurov, Moscow (RU); and Jia Xie, San Diego, CA (US)
Assigned to HESPERIX SA, Viganello (CH); and THE SCRIPPS RESEARCH INSTITUTE, La Jolla, CA (US)
Filed by HESPERIX SA, Viganello (CH); and THE SCRIPPS RESEARCH INSTITUTE, La Jolla, CA (US)
Filed on Jul. 26, 2021, as Appl. No. 17/385,834.
Application 17/385,834 is a continuation of application No. 16/983,491, filed on Aug. 3, 2020, granted, now 11,215,618.
Application 16/983,491 is a continuation of application No. 16/753,635, abandoned, previously published as PCT/RU2018/000653, filed on Oct. 4, 2018.
Claims priority of application No. RU2017134483 (RU), filed on Oct. 4, 2017; and application No. RU2018112009 (RU), filed on Apr. 4, 2018.
Prior Publication US 2022/0018845 A1, Jan. 20, 2022
Int. Cl. G01N 33/574 (2006.01); A61K 35/17 (2015.01); A61K 39/00 (2006.01); C07K 16/28 (2006.01); C12Q 1/6886 (2018.01); G01N 33/50 (2006.01); G01N 33/543 (2006.01)
CPC G01N 33/57492 (2013.01) [A61K 35/17 (2013.01); A61K 39/0011 (2013.01); C07K 16/2803 (2013.01); C12Q 1/6886 (2013.01); G01N 33/505 (2013.01); G01N 33/543 (2013.01); A61K 2039/5156 (2013.01); A61K 2039/5158 (2013.01); A61K 2039/54 (2013.01); C07K 2317/24 (2013.01); C07K 2317/53 (2013.01); C07K 2317/73 (2013.01); C07K 2319/03 (2013.01); C07K 2319/33 (2013.01); C12Q 2600/156 (2013.01)] 10 Claims
 
1. A method of treating lymphoma in a human subject comprising:
identifying a unique B cell receptor expressed in clonally related malignant lymphoma cells of the subject;
modifying a population of T cells by introducing nucleic acid molecules encoding the the unique B cell receptor and nucleic acid molecules encoding a library of CARs wherein each CAR within the library comprises extracellular antigen binding domain comprising a distinct putative ligand of a unique B cell receptor, wherein the T cells co-express the unique B cell receptor and a CAR from the library on the cell surface;
measuring activation of the T cells in response to autocrine CAR signaling induced by binding of the putative ligand of the CAR to the co-expressed unique B cell receptor, thereby identifying a ligand of the unique B cell receptor ligand; and
administering to the subject a therapeutically effective amount of the ligand of the unique B cell receptor coupled to an immunotherapeutic agent, wherein the putative ligand of the unique B cell receptor is a peptide, a cyclopeptide, or a VHH.