US 11,860,163 B2
Methods and compositions for identifying and treating subjects at risk for poor CAR T cell therapy response
Melody Smith, New York, NY (US); Marcel van den Brink, New York, NY (US); Eric Pamer, Montclair, NJ (US); and Eric Littmann, Brooklyn, 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 Apr. 13, 2021, as Appl. No. 17/229,184.
Application 17/229,184 is a continuation of application No. PCT/US2019/056137, filed on Oct. 14, 2019.
Claims priority of provisional application 62/754,347, filed on Nov. 1, 2018.
Claims priority of provisional application 62/745,343, filed on Oct. 13, 2018.
Prior Publication US 2021/0231657 A1, Jul. 29, 2021
Int. Cl. G01N 33/569 (2006.01); A61K 35/17 (2015.01); A61K 35/74 (2015.01)
CPC G01N 33/56911 (2013.01) [A61K 35/17 (2013.01); A61K 35/74 (2013.01); G01N 2496/00 (2013.01); G01N 2800/52 (2013.01)] 15 Claims
 
1. A method for treating a subject having a cancer, comprising:
(i) (a) determining the level of a bacterium or spores thereof in a sample of the subject;
(b) comparing the level of the bacterium or spores thereof to a reference bacterium or spores thereof level, wherein the reference bacterium or spores thereof level is a level of the bacterium or spores thereof in a patient that had a CAR T cell therapy response;
(c) identifying the subject as likely to have a response to a CAR T cell therapy, or as likely to have no response or a poor response to the CAR T cell therapy, based on the comparison; and
(d) administering the CAR T cell therapy to the subject identified as likely to have a response to the CAR T cell therapy, or administering a therapeutic bacterium or spores thereof or a pharmaceutical comprising thereof to the subject identified as likely to have no response or a poor response to the CAR T cell therapy,
wherein the bacterium is selected from the group consisting of bacteria of the Peptostreptococcaceae family, bacteria of the Bacteroidaceae family, bacteria of the Clostridiaceae family, bacteria of the Lachnospiraceae family, bacteria of the Rikenellaceae family, bacteria of the Lactobacillaceae family, bacteria of the Oscillospiraceae family, bacteria of the Ruminococcaceae family, bacteria of the Acidaminococcaceae family, bacteria of the Peptococcaceae family and combinations thereof; and/or
(ii) (a) determining the level of a bacterial gene in a sample of the subject;
(b) comparing the level of the bacterial gene to a reference bacterial gene level, wherein the reference bacterial gene level is a level of the bacterial gene in a patient that had a CAR T cell therapy response;
(c) identifying the subject as likely to have a response to a CAR T cell therapy, or as likely to have no response or a poor response to the CAR T cell therapy, based on the comparison; and
(d) administering the CAR T cell therapy to the subject identified as likely to have a response to the CAR T cell therapy, or administering a therapeutic bacterium or spores thereof or a pharmaceutical comprising thereof to the subject identified as likely to have no response or a poor response to the CAR T cell therapy,
wherein the bacterial gene is selected from the group consisting of genes involved in vitamin B biosynthesis or secondary bile acid biosynthesis or degradation.