IP Library › Granted Patent US 12,551,515
Granted Patent B2
US 12,551,515 · App. 17/296,072 · Granted Feb 17, 2026

Methods and compositions for treating cancer

Inventors: Jennifer A. Wargo (Houston, TX); Vancheswaran Gopalakrishnan (Houston, TX); Miles C. Andrews (Victoria, AU); Laurence Zitvogel (Villejuif, FR); Valerio Iebba (Villejuif, FR)
Assignees: Board of Regents of the University of Texas System; Institut Gustave Roussy
A61K35/747A61K35/741A61K39/3955A61P35/00C12Q1/689A61K2039/505C07K16/2818C07K16/2827C12Q2600/106
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Quick Facts
Patent No.
US 12,551,515
App. No.
17/296,072
Granted
Feb 17, 2026
Kind
B2
Abstract

Described herein are methods and compositions for treating cancer and for predicting a subjects' response to combination checkpoint inhibitor therapy. Aspects of the disclosure relate to a method of treating cancer and/or reducing toxicity to a therapy in a subject comprising administering to the subject a composition comprising at least one isolated or purified population of bacteria belonging to one or more of the genera Flavonifractor, Dielma, Akkermansia, Alistipes, Bacteroides, Butyricimonas, Vampirovibrio, Tyzzerella, Parabacteroides distasonis, Fournierella, Fournierella massiliensis, Eisenbergiella tayi, Tissierellales, Hungateiclostridium thermocellum, Dorea formicigenerans, Caloramator coolhaasi, Muricomes, Geosporobacter, Prevotella paludivivens, Lactobacillus secaliphilus, Bacteroides finegoldii, Lactobacillus johnsonii, Parapedobacter composti , and Anaerotignum lactatifermentans and wherein the method further comprises treating the subject with a combination of (i) a PD-1, PDL1, or PDL2 inhibitor and (ii) a CTLA-4, B7-1, CN or B7-2 inhibitor.

Claims (13)

1 . A method of treating melanoma in a subject comprising: administering to a subject determined to have a microbial profile comprising Bacteroides fragilis, Vampirovibrio , and Tyzzerella in the gut microbiome, a combination of (i) a PD-1, PD-L1, or PD-L2 inhibitor and (ii) a CTLA-4, B7-1, or B7-2 inhibitor.

2 . The method of claim 1 , wherein the melanoma is metastatic melanoma, Lentigo Maligna, Superficial Spreading Melanoma, Nodular Melanoma, Acral Lentiginous Melanoma, Cutaneous Melanoma, or Desmoplastic Melanoma.

3 . The method of claim 2 , wherein the melanoma comprises Cutaneous Melanoma.

4 . The method of claim 1 , wherein the method further comprises administering at least one additional anticancer treatment and wherein the at least one additional anticancer treatment is surgical therapy, chemotherapy, radiation therapy, hormonal therapy, immunotherapy, small molecule therapy, receptor kinase inhibitor therapy, anti-angiogenic therapy, cytokine therapy, cryotherapy or a biological therapy.

5 . The method of claim 1 , wherein the inhibitor of (i) is an anti-PD-1 monoclonal antibody and (ii) is an anti-CTLA-4 monoclonal antibody.

6 . The method of claim 5 , wherein (i) comprises nivolumab, pembrolizumab, or pidilizumab and/or wherein (ii) comprises ipilimumab or tremelimumab.

7 . The method of claim 1 , wherein the cancer comprises stage III or IV cancer.

8 . The method of claim 1 , wherein the subject is a human subject.

9 . The method of claim 1 , wherein the microbial profile for the subject was determined by analyzing the microbiome in a sample from the subject.

10 . The method of claim 9 , wherein the sample is a fecal sample.

11 . The method of claim 9 , wherein analyzing comprises performing 16S ribosomal sequencing and/or metagenomics whole genome sequencing.

12 . The method of claim 1 , wherein the subject has previously been treated for melanoma.

13 . The method of claim 1 , wherein the melanoma is recurrent.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 6, 2022
From: ZITVOGEL, LAURENCE; IEBBA, VALERIO
To: INSTITUT GUSTAVE ROUSSY
Reel/Frame 058580/0714 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 6, 2022
From: WARGO, JENNIFER A.; GOPALAKRISHNAN, VANCHESWARA; ANDREWS, MILES C.
To: BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM
Reel/Frame 058583/0648 →
Continuity (3)
Provisional Application 62770603 · Nov 21, 2018
Provisional Application 62826631 · Mar 29, 2019
Related Publication 20220016188A1 · Jan 20, 2022
References Cited (132)
US 20160193257A1 · Honda et al. · 2016 [cited by applicant]
US 20180243351A1 · Hlavka · 2018 [cited by applicant]
US 20180273940A1 · Sommer · 2018 [cited by examiner]
US 20180303934A1 · Clube et al. · 2018 [cited by applicant]
US 20200129569A1 · Wargo et al. · 2020 [cited by applicant]
CA 2987129 · 2015 [cited by applicant]
CN 105296590 · 2016 [cited by applicant]
CN 108884159 · 2018 [cited by applicant]
EP 3411052 · 2020 [cited by applicant]
WO WO1995001994 · 1995 [cited by applicant]
WO WO1996015660 · 1996 [cited by applicant]
WO WO1998042752 · 1998 [cited by applicant]
WO WO2000037504 · 2000 [cited by applicant]
WO WO2001014424 · 2001 [cited by applicant]
WO WO2005003168 · 2005 [cited by applicant]
WO WO2005009465 · 2005 [cited by applicant]
WO WO2006000317 · 2006 [cited by applicant]
WO WO2006072625 · 2006 [cited by applicant]
WO WO2006072626 · 2006 [cited by applicant]
WO WO2006121168 · 2006 [cited by applicant]
WO WO2007042573 · 2007 [cited by applicant]
WO WO2008084106 · 2008 [cited by applicant]
WO WO2008132601 · 2008 [cited by applicant]
WO WO2009044273 · 2009 [cited by applicant]
WO WO2009101611 · 2009 [cited by applicant]
WO WO2009114335 · 2009 [cited by applicant]
WO WO2010027827 · 2010 [cited by applicant]
WO WO2010065939 · 2010 [cited by applicant]
WO WO2011008369 · 2011 [cited by applicant]
WO WO2011014438 · 2011 [cited by applicant]
WO WO2011066342 · 2011 [cited by applicant]
WO WO2011094027 · 2011 [cited by applicant]
WO WO2012071411 · 2012 [cited by applicant]
WO WO2012160448 · 2012 [cited by applicant]
WO WO2013006490 · 2013 [cited by applicant]
WO WO2013025779 · 2013 [cited by applicant]
WO WO2013067492 · 2013 [cited by applicant]
WO WO2014022021 · 2014 [cited by applicant]
WO WO2015016718 · 2015 [cited by applicant]
WO WO2015066625 · 2015 [cited by applicant]
WO WO2015075688 · 2015 [cited by applicant]
WO WO2015095241 · 2015 [cited by applicant]
WO WO2015153639 · 2015 [cited by applicant]
WO WO2016063263 · 2016 [cited by applicant]
WO WO2016196605 · 2016 [cited by applicant]
WO WO2017172894 · 2017 [cited by applicant]
WO 2018026913 · 2018 [cited by applicant]
WO 2018064165 · 2018 [cited by applicant]
WO WO2018115519 · 2018 [cited by applicant]
WO 2019099482 · 2019 [cited by applicant]
WO 2019152667 · 2019 [cited by applicant]
WO 2019178494 · 2019 [cited by applicant]
WO WO2019191390 · 2019 [cited by applicant]
Falony et al. 2016. Science. 352(6285):560-564 (Year: 2016). [cited by examiner]
Pevsner-Fischer et al. Apr. 10, 2016. World J Clin Oncol. 7(2):200-213. (Year: 2016). [cited by examiner]
Amaral et al. Expert Opin Pharmacother. 2017. 18(7): 689-699 (Year: 2017). [cited by examiner]
Elkrief et al. OncoImmunology. 2019. 8(4):e1568812 (Year: 2019). [cited by examiner]
Derosa. Ann Oncol. 2018. 29: 1437-1444 (Year: 2018). [cited by examiner]
National Cancer Institute. Cancer Staging. Retrieved from the Internet on Nov. 19, 2024 at <URL:https://www.cancer.gov/about-cancer/diagnosis-staging/staging> (Year: 2024). [cited by examiner]
Yun et al. Cancer Medicine. 2016. 5(7):1481-1491 (Year: 2016). [cited by examiner]
Shahinas et al. 2012. mBio. 3(5): e00338-12 (Year: 2012). [cited by examiner]
Zhang. 2018. Protein Cell. 9(5):462-473. (Year: 2018). [cited by examiner]
Berger, et al. “Flavonifractor (Eubacterium) plautii bloodstream infection following acute cholecystitis”, [cited by applicant]
National Cancer Institute, Common Terminology Criteria for Adverse Events (CTCAE), 2017. [cited by applicant]
Office Action issued in corresponding Chinese Application No. 202080019540.8 dated Oct. 17, 2023. [cited by applicant]
Office Action issued in corresponding European Application No. 20740867 dated May 22, 2023. [cited by applicant]
Office Action issued in corresponding Japanese Application No. 2021529087, dated Nov. 20, 2023. [cited by applicant]
Prados et al., “Regression of established subcutaneous B16-F10 murine melanoma tumors after gef gene therapy associated with the mitochondrial apoptotic pathway”, [cited by applicant]
Rudzki, J. “Management of adverse events related to checkpoint inhibition therapy”, [cited by applicant]
Wang et al., “Fecal microbiota transplantation for refractory immune checkpoint inhibitor-associated colitis”, [cited by applicant]
Wen et al.., “Research progress of intestinal flora and ulcerative colitis”, [cited by applicant]
Nordenberg, et al., “Growth Inhibitions of Murine Melanoma by Butyric Acid and Dimethysulfoxide”, [cited by applicant]
Office Action and Search Report in corresponding Chinese Application No. 201780072679.7, dated Jan. 17, 2022 (English Translation). [cited by applicant]
Wang et al., “Current Treatment Status and Progress of Anti-PD-1 Antibody Therapy for Advanced Melanoma”, [cited by applicant]
Office Action issued in corresponding European Application 20740867 dated May 22, 2023. [cited by applicant]
Eichele et al. “Dextran sodium sulfate colitis murine model: An indispensable tool for advancing our understanding of inflammatory bowel diseases pathogenesis”, [cited by applicant]
Final Office Action issued in corresponding U.S. Appl. No. 17/422,719, dated Mar. 8, 2024. [cited by applicant]
Lo et al. “Immune checkpoint inhibitor-induced colitis is mediated by polyfunctional lymphocytes and is dependent on an IL23/IFNy axis”, [cited by applicant]
Durnov L.A. et al., Pediatric Oncology. [cited by applicant]
Extended Search Report issued in related European Patent Application No. 19886594.1, dated Oct. 24, 2022. [cited by applicant]
Office Action issued in related Russian Patent Application No. 2019108925, dated Jul. 4, 2022. [cited by applicant]
Brief Medical Encyclopedia, Renal Stone Disease—Substance Dependencies. [cited by applicant]
Karimi, G. et al., “Single-species versus dual-species probiotic supplementation as an emerging therapeutic strategy for obesity”, [cited by applicant]
Kamiya, S., “Intestinal Disease, Liver Disease”, [cited by applicant]
Office Action issued in corresponding Canadian Application No. 3038076, dated Jan. 16, 2024. [cited by applicant]
Office Action issued in corresponding Japanese Application No. 2019516669, dated Nov. 28, 2023. (English Translation Provided). [cited by applicant]
Ohno, K. et al., “Microbiome therapy (bacteria transplant, fecal microorganism transplant)”, [cited by applicant]
Abu-Sbeih H et al., Importance of endoscopic and histological evaluation in the management of immune checkpoint inhibitor-induced colitis. [cited by applicant]
Adler, B et al., Histopathological and immunophenotypic features of ipilimumab-associated colitis compared to ulcerative colitis. [cited by applicant]
Berman, D et al., Blockade of cytotoxic T-lymphocyte antigen-4 by ipilimumab results in dysregulation of gastrointestinal immunity in patients with advanced melanoma. [cited by applicant]
Choi K et al., Can Immune Checkpoint Inhibitors Induce Microscopic Colitis or a Brand New Entity? [cited by applicant]
Thomas A et al., Immune Checkpoint Inhibitor Enterocolitis vs Idiopathic Inflammatory Bowel Disease. [cited by applicant]
Wang Y et al., Endoscopic and Histologic Features of Immune Checkpoint Inhibitor-Related Colitis. [cited by applicant]
Borody et al. “Fecal microbiota transplantation and emerging applications” Nat. Rev. Gastroenterol. & Hepatol. 2011, 9, 88-96. [cited by applicant]
Bultman, et al., “Microbial-Derived Butyrate: Oncometabolite or Tumor-Suppressive Metabolite?” Cell Host & Microbe, 16: 143-145, 2014. [cited by applicant]
Chaput et al., “Baseline gut micro biota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab.” [cited by applicant]
Chen et al., “Analysis of Immune Signatures in Longitudinal Tumor Samples Yields Insight into Biomarkers of Response and Mechanisms of Resistance to Immune Checkpoint Blockade.” [cited by applicant]
Dubin et al., “Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis.” [cited by applicant]
Extended European Search Report Issued in Corresponding European Patent Application No. 17857329.1, dated Aug. 7, 2020. [cited by applicant]
Frankel, et al., “Metagenomic Shotgun Sequencing and Unbiased Metabolomic Profiling Identify Specific Human Gut Microbiota and Metabolites Associated with Immune Checkpoint Therapy Efficacy in Melanoma Patients,” [cited by applicant]
Garrett, “Cancer and the Microbiota,” [cited by applicant]
Gopalakrishnan et al., “Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients.” [cited by applicant]
Gueimonde, et al., “Antibiotic Resistance in Probiotic Bacteria,” Frontiers in Microbiology, 4(202): 1-6, 2013. [cited by applicant]
International Search Report and Written Opinion Issued in Corresponding PCT Patent Application No. PCT/US2017/053717, mailed Feb. 2, 2018. [cited by applicant]
International Search Report and Written Opinion Issued in Corresponding PCT Patent Application No. PCT/US2019/024519, dated Oct. 24, 2019. [cited by applicant]
International Search Report and Written Opinion Issued in Corresponding PCT Patent Application No. PCT/US2019/62659, mailed Mar. 30, 2020. [cited by applicant]
International Search Report and Written Opinion Issued in Corresponding PCT Patent Application No. PCT/US2020/013808, mailed Jun. 2, 2020. [cited by applicant]
Jenq et al., “Intestinal Blautia Is Associated with Reduced Death from Graft-versus-Host Disease” Biol. Blood Marrow Transplant. 2015, 21, 1373-1383. [cited by applicant]
Klieve, et al., “Ruminococcus Bromii, Identification and Isolation as a Dominant Community Member in the Rumen of Cattle Fed A Barley Diet,” Journal of Applied Microbiology, 103: 2065-2073, 2007. [cited by applicant]
Litvak et al., “Dysbiotic Proteobacteria expansion: a microbial signature of epithelial dysfunction” J. Curr. Opin. Microbiol. 2017, 39, 1-6. [cited by applicant]
Maronpot et al., “Relevance of Animal Carcinogenesis Findings to Human Cancer Predictions and Prevention” [cited by applicant]
Matson et al., “The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients.” [cited by applicant]
Miquel et al., “Faecalibacterium prausnitzii and human intestinal health” [cited by applicant]
Moco, et al., “Metabolomics View on Gut Microbiome Modulation by Polyphenol-Rich Foods,” [cited by applicant]
Patyar et al., “Bacteria in cancer therapy: a novel experimental strategy” [cited by applicant]
Pitt, et al., “Fine-Tuning Cancer Immunotherapy: Optimizing the Gut Microbiome,” [cited by applicant]
Pitt, et al., “Resistance Mechanisms to Immune-Checkpoint Blockade in Cancer: Tumor-Intrinsic and -Extrinsic Factors,” Immunity, 44(6), 1255-1269, 2016. [cited by applicant]
Png et al., “Mucolytic Bacteria With Increased Prevalence in IBD Mucosa Augmentin VitroUtilization of Mucin by Other Bacteria” [cited by applicant]
Poutahidis Theofilis, et al., “Gut Microbiota and the Paradox of Cancer Immunotherapy,” [cited by applicant]
Roh et al., “Integrated molecular analysis of tumor biopsies on sequential CTLA-4 and PD-1 blockade reveals markers of response and resistance.” [cited by applicant]
Routy et al., “Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors.” [cited by applicant]
Segata et al., “Metagenomic biomarker discovery and explanation.” [cited by applicant]
Sivan, et al., “Commensal Bifidobacterium Promotes Antitumor Immunity and Facilitates Ant-PD-L1 Efficacy,” [cited by applicant]
Smelt, et al., “Probiotics Can Generate FoxP23 T-Cell Responses in the Small Intestine an Simultaneously CD4 and CD8 T Cell Activation in the Large Intestine,” Plos One, 8(7):e68952, 1-12, 2013. [cited by applicant]
Taur, et al., “The Effects of Intestinal Tract Bacterial Diversity on Mortality Following Allogenic Hematopoietic Stem Cell Transplantation,” [cited by applicant]
Tumeh, et al., “PD-1 Blockade Induces Responses by Inhibiting Adaptive Immune Resistance,” [cited by applicant]
Vétizou et al., “Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota.” [cited by applicant]
Viaud, et al., “Gut Microbiome and Anticancer Immune Response: Really Hot Sh*t!” Cell Death and Differentiation, 22(2): 199-214, 2014. [cited by applicant]
Wang et al., “Bifidobacterium can mitigate intestinal immunopathology in the context of CTLA-4 blockade.” [cited by applicant]
Wang et al., “P038 Fecal Microbiota Transplant (FMT) For Immuno-checkpoint Inhibitor-Induced Colitis (ICI-C) In A 50 Year Old Female With Bladder Cancer” [cited by applicant]
Wei et al., “Bacterial targeted tumour therapy-dawn of a new era” [cited by applicant]
Extended European Search Report in corresponding EP Application No. 20740867.5, dated Aug. 11, 2022. [cited by applicant]