Microbiome in Immuno-Oncology

Cambridge Healthtech Institute 第1回

第15回Discovery on Targetの一翼を担うイベント


Final Agenda

7:00 am Registration Open and Morning Coffee

Mechanisms of Immune System-Directed Therapies for Cancer

7:55 Welcome Remarks

Cindy Crowninshield, RDN, LDN, HHC, Senior Conference Director, Cambridge Healthtech Institute

8:00 Chairperson's Opening Remarks

William Loging, Ph.D., Associate Professor of Genomics & Head, Production Bioinformatics, Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai; Editor, Bioinformatics and Computational Biology in Drug Discovery and Development

8:10 Targeting the Microbiome in I/O

Rodolphe Clerval, Chief Business Officer, Vice President US Operations, Enterome Bioscience

Enterome discovers and develops microbiome derived molecules in immunology (IBD & I/O). Our approach is based on complete genetic and functional analysis of the microbiome. First clinical product candidate in IBD based on novel disease-modifying mechanism of action.

8:40 Molecular Impacts of Immune Modulating Drugs on Cancer Patients

William Loging, Ph.D., Associate Professor of Genomics & Head, Production Bioinformatics, Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai; Editor, Bioinformatics and Computational Biology in Drug Discovery and Development, Cambridge University Press, 2016

The area of Immuno-Oncology provides a novel strategy for cancer treatment by utilizing the patient's immune system to combat tumor growth. We investigated the impact of specific immune modulating drugs on patients with diagnosed tumors in order to understand the molecular changes that take place at the pathway level. These data are correlated to phenotypic effect and provide insights into the mechanism of immune system directed therapies for cancer.

9:10 Presentation to be Announced

9:40 Networking Coffee Break with Poster Viewing

10:10 The Breast Tissue Microbiome: Associations with Cancer and Cancer Risk

Tina Hieken, M.D., Surgical Oncologist and Associate Professor of Surgery, Mayo Clinic College of Medicine
The complex microenvironment of breast tissue includes epithelium, stroma and a mucosal immune system providing evidence for an intrinsic breast tissue microbiome. Our recently published data using culture-independent genomic analysis of sterile human breast tissue confirms the existence of a breast tissue microbiome, distinct from other body niches. We assessed breast tissue microbial signatures in intraoperatively obtained samples using 16SrDNA hypervariable tag sequencing, along with simultaneously aseptically collected skin tissue and skin swab samples. Our results indicate a distinct breast tissue microbiome different from the microbiota of skin tissue, surface breast skin swabs and buccal swabs. Further, we found distinct microbial communities in breast tissues from women with breast cancer vs women with benign disease. Malignancy correlated with enrichment in taxa of lower abundance including the genera Fusobacterium, Atopobium, Gluconacetobacter, Hydrogenophaga and Lactobacillus. Testing for confounding showed no significant effect of age and menopausal status (MiRKAT P>0.05) indicating the differences were not driven by these factors. Fusobacterium is reported in other epithelial malignancies and may act by secreting virulence factors as well as creating a pro-inflammatory environment promoting carcinogenesis. Therefore, we investigated the functional role of the breast tissue microbiome within these microenvironments. Using KEGG pathways, we identified 6 as differentially abundant between benign vs malignant disease states. In patients with breast cancer, pathways involving cysteine and methionine metabolism, glycosyltransferases, fatty acid biosynthesis and C5-branched dibasic acid metabolism were depleted. Mammographic breast density (MBD) is a well-established breast cancer risk factor conferring a 2 to 4-fold elevated risk in women with heterogeneously or extremely dense breasts. As bacterial communities influence immune-mediated inflammatory changes that affect stroma in ways that may affect breast carcinogenesis, we further explored how microbial composition within breast tissue might correlate with MBD. For BI-RADS density defined as high or low we saw a trend toward lower alpha diversity in high-MBD samples (linear regression P=0.13 for observed OTU number, P=0.23 for Shannon index). Beta-diversity analysis showed a significant association on weighted (MiRKAT P=0.049) but not unweighted UniFrac distance (MiRKAT P=0.31), indicating a MBD association with community composition (taxa abundance) rather than structure (taxa presence or absence). Boruta feature selection identified two genera from the phylum Actinobacteria, Corynebacterium and Actinomyces, as most predictive of MBD suggesting a microbiome component of MBD-associated breast cancer risk.

10:40 Presentation to be Announced

11:10 Sponsored Presentation (Opportunity Available)

11:40 Enjoy Lunch on Your Own

Influences of Inflammation and Nutrition in Microbiome and Cancer

1:10 pm Chairperson's Remarks

Bonnie Feldman, D.D.S., MBA, Digital Health Analyst and Chief Growth Officer, DrBonnie360

1:20 Alimentary Effect in Microbiome and Cancer

Antonio Rezusta, Professor, Section Head, Microbiology, Hospital Universitario Miguel Servet

This presentation discusses microbiota management in the prevention and treatment of cancer. Topics covered will include 1) the interest in knowing which microorganisms favor colon cancer, 2) the influence that can modify the microbiota in the prevention of cancer, 3) the influence that modifying the flora can have on the response to chemotherapy, and 4) the consequences for any cancer treatment of antimicrobial resistance.

1:50 Influences of Inflammation, Vitamin D Receptor, and Gut Microbiome in Cancers

Jun Sun, Ph.D., AGA Fellow, Associate Professor, Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago

Vitamin D deficiency is implicated in the pathology of over 17 types of cancers. Vitamin D exerts its regulatory roles in immunity, host defense, and inflammation via vitamin D receptor (VDR). We have demonstrated that VDR deletion leads to dysbiosis and human VDR gene variation shapes gut microbiome. Here, we will discuss influences of inflammation, VDR, and microbiome in cancers.

2:20 Microbial Allies across the Cancer Continuum:  Getting to Know Our Fiber-Fermenting Friends

Carrie R. Daniel-MacDougall, Ph.D., MPH, Assistant Professor, Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center

The gut microbiome's role in inflammation, immunity, and carcinogenesis extends beyond specific pathogens to the wider community of beneficial, commensal bacteria, nurtured by fiber and resistant starch-rich "prebiotic" plant foods (e.g., Faecalibacterium prausnitzii, Roseburia and Ruminococcus species). Building on longstanding, evidence-based dietary recommendations for chronic disease prevention, targetable diet-microbiota relationships stand at the interface of cancer prevention, treatment, and survival strategies.

2:50 Networking Refreshment Break with Poster Viewing

Promising Applications in Therapeutic Oncology: Current Practices and Emerging Platforms, Devices, and Therapies

3:30 Next-Generation Immunotherapeutics from the Microbiome: Amrita Therapeutics' Oncology Peptides

Susan K. Finston, Esq., CEO and Managing Director, Amrita Therapeutics

Amrita's mission is to offer cancer patients new and better oncology peptides and implantable therapeutic devices to combat cancer without the immunogenicity/toxicity of current bacterial immunotherapeutics. Research thus far has focused mainly on peptides and proteins related to Mycobacterium Tuberculosis (M. bovis), an early success story for oncology immunotherapy, with preeminent effectiveness of bacillus Calmette-Guerin (BCG) to treat bladder cancer. Amrita Therapeutics is the first company to study the therapeutic efficacy of individual proteins and peptides related to M. bovis and now has received its first U.S. patent for novel modified, truncated peptides.

4:00 Targeting Microbial b-Glucuronidases with Symbiotic Drugs to Improve Cancer Therapy

Bret Wallace, Ph.D., Scientist, Symberix, Inc.

Many toxic compounds are inactivated by liver cells and subsequently reactivated by gut microbiota. We recently showed that E. coli GUS is one of several structurally distinct b-glucuronidases expressed in the human gut microbiome (i.e., human GUSome). We describe here potential uses of new symbiotic drugs that target harmful components of the human GUSome to improve cancer therapy. This includes prevention of chemotherapy-induced diarrhea, improvement of chemotherapy survival outcomes, and cancer prevention. The GUSome is an emerging platform of druggable microbiome targets with promising applications in therapeutic oncology.

4:30 KEYNOTE PRESENTATION: Microbiome Therapeutics in Immuno-Oncology: Current Practices to Future Therapies

Zain Kassam, M.D., MPH, FRCPC, CMO, OpenBiome; Gastroenterologist, Epidemiologist and Research Affiliate, MIT Center for Microbiome Informatics & Therapeutics

5:00 Close of Symposium

5:00 Pre-Conference Dinner Short Course Registration

Click here for details on short courses offered.

* 不測の事態により、事前の予告なしにプログラムが変更される場合があります。

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