Methods and compositions for identifying and treating subjects at risk for checkpoint blockade therapy associated colitis
a technology of colitis and checkpoint blockade, which is applied in the field of methods and compositions for identifying and treating subjects at risk of checkpoint blockade therapy associated colitis, can solve the problems of unhelpful or harmful effects that remain difficult to achieve, and it is difficult to define the composition of the intestinal microbiome that precedes the development of colitis, so as to achieve the effect of increasing fecal abundan
Inactive Publication Date: 2021-12-02
MEMORIAL SLOAN KETTERING CANCER CENT
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AI Technical Summary
Benefits of technology
This approach allows for the accurate identification of subjects at higher or lower risk for checkpoint blockade therapy-associated colitis and provides therapeutic compositions that can reduce the risk or severity of colitis by modulating the intestinal microbiome, thereby facilitating preemptive treatments.
Problems solved by technology
Identifying the microbial species that promote homeostasis or other healthy benefits and those that drive inflammation or have other unhelpful or harmful effects has remained difficult to do in the clinical context, particularly with chronic inflammatory conditions such as Inflammatory Bowel Disease (IBD).
Thus, as most patients seek medical attention after inflammation has developed, it is difficult to define the microbiota composition of the intestinal microbiome that precedes the development of colitis.
Method used
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[0118]The presently disclosed subject matter will be better understood by reference to the following Examples, which are provided as exemplary of the invention, and not by way of limitation.
[0119]Checkpoint blockade therapy may be referred to in these examples as “CTL4 blockade.”
6.1 Methods—Specimen DNA Preparation, Sequencing, and Statistical Analyses
[0120]The following methods were used in connection with the remaining examples.
[0121]6.1(a) Study Patients and Specimen Collection from Patients Receiving Checkpoint Blockade Therapy
[0122]Fecal samples of 34 adult patients diagnosed with metastatic melanoma who received ipilimumab checkpoint blockade therapy at Memorial Sloan-Kettering Cancer Center (MSKCC) were collected. For 30 patients, fecal samples were collected from each patient prior to the first administration of ipilimumab; for 2 patients who developed gastrointestinal inflammation and 2 who remained inflammation free, samples were collected after administration of ipilimuma...
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The present invention relates to methods and compositions for identifying subjects treated with or considered for treatment with checkpoint blockade therapeutic agents that are at higher or lower risk for developing checkpoint therapy associated colitis, by analyzing the intestinal microbiome of those subjects. It is based, at least in part, on the discovery that the abundance of certain intestinal microbiota of the phyla Bacteroidetes, including the bacteria in the families Bacteroidaceae, Rikenellaceae, and Barnesisllaceae, and / or an increase or decrease in microbial genetic pathways involved in polyamine transport and / or B vitamin biosynthesis (e.g., (riboflavin (B2), pantothenate (B5) and thiamine (B1)) are associated with the likelihood of developing checkpoint therapy associated colitis.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a divisional of U.S. patent application Ser. No. 15 / 984,613, filed May 21, 2018, which is a continuation application of International application PCT / US2016 / 063530, filed Nov. 23, 2016, which claims priority to U.S. Provisional Application No. 62 / 259,445, filed on Nov. 24, 2015, the contents of each which are incorporated by reference in their entirety herein, and to each of which priority is claimed.STATEMENT OF GOVERNMENT INTEREST[0002]This invention was made with government support under AI042135 and CA008748 awarded by the National Institutes of Health. The government has certain rights in the invention.SEQUENCE LISTING[0003]The instant application contains a Sequence Listing which has been filed electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Jun. 14, 2021, is named 072734_1259_SL.txt and is 1,128 bytes in size. The Sequence Listing does not exten...
Claims
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IPC IPC(8): A61K35/742A61K45/06G01N33/569A23L5/00A61P1/00A61K9/00
CPCA61K35/742A61K45/06G01N33/56911A23L5/00A61K2035/115A61K9/0031A61K9/0043A61K9/0053G01N2800/067A61P1/00
InventorPAMER, ERICWOLCHOK, JEDD D.DUBIN, KRISTA
OwnerMEMORIAL SLOAN KETTERING CANCER CENT