Cambridge Healthtech Institute’s Inaugural

The Microbiome in Cancer Immunotherapy

Exploring the Role of the Microbiome in Cancer
and Immune Response

December 5-6, 2017 | Hilton San Diego Resort | San Diego, CA

 

Cancer immunotherapies are an exciting treatment option, harnessing the body’s immune system to target cancer cells. However, not all patients respond to these treatments. There are myriad reasons for this, but it is becoming more apparent that the microbiome plays a bigger role than previously thought. At Cambridge Healthtech Institute’s Inaugural Microbiome in Cancer Immunotherapy conference, leading researchers from microbiology and immunology will come together to address the impact the microbiome can have on this emerging area of therapy. Multiple strategies will be addressed, including more traditional approaches, such as transplanting the gut microbiome to boost immunotherapy response, as well as newer strategies, such as supplementing the microbiome to increase response. Overall, this event will provide an in-depth look at an emerging, yet critical, area of study to continue moving immunotherapies to the clinic.

Final Agenda

Recommended Pre-Conference Short Courses*

SC1: Omic Technology for Cancer Immuno-Oncology

SC2: Applications of a Quantitative Imaging Tool Box in Evaluating a CAR Immune Synapse and Contributing to Rational CAR Design

*Separate registration required

TUESDAY, December 5

7:30 am Registration and Morning Coffee

INNOVATION IN IMMUNOTHERAPY-MICROBIOME RESEARCH

8:30 Chairperson's Opening Remarks

8:35 KEYNOTE PRESENTATION: Cancer Immunotherapy and the Microbiome – Intersection of the Gut Microbiota and Immune System

maiti arpitaArpita Maiti, PhD, Senior Director, External Science & Innovation, Inflammation & Immunology and Microbiome, Pfizer Inc.

Interactions between gut microbiota and the immune system are important for immune system development and peripheral tolerance. It is therefore intriguing to hypothesize that the intersection of the microbiome and immune cells in the gut is the key to gaining a mechanistic understanding of how the microbiome impacts the mobilization of immune cells via checkpoint blockade. This understanding may provide a rich source of adjunctive and combination microbiome-based therapies that could increase the rates of patients responding to immunotherapies based on taking the “brakes” off immune cells.

9:05 Mycobiome (Fungal Microbiome) in Cancer Immunotherapy

Pranab_MukherjeePranab Mukherjee, MSc, Ph.D., Associate Professor, Dermatology, Case Western Reserve University

Fungi are integral components of the human microbiome, however this fungal microbiome ("Mycobiome") has attracted far less attention than the bacterial microbiome. Recent studies have demonstrated that fungi induce specific interactions with bacteria and the host, thus affecting health and disease. Our group has conducted studies showing that fungal mycobiome plays a critical role in skin diseases like atopic dermatitis and psoriasis, as well as in the setting of inflammatory bowel disease and HIV infection.

9:35 The Skin Microbiome and its Role In Cutaneous Squamous Cell Carcinoma Progression

Anita_VoigtAnita Y Voigt, Ph.D., Post-Doctoral Researcher, The Jackson Laboratory for Genomic Medicine

The skin microbiome plays a critical role in homeostasis of the skin and the modulation of the immune system. Changes in the microbiome can play a role in skin disorders. We are investigating the connection with skin cancer development and progression in humans and mice and the beneficial or detrimental effects of certain microbes on the tumor development. Furthermore, we explore the diagnostic potential of the microbiome for skin cancer.

10:05 Coffee Break in the Exhibit Hall with Poster Viewing

UNDERSTANDING THE MICROBIOME IN IMMUNOTHERAPY

10:50 Targets and Pitfalls of the Microbiome during Immunotherapy

Julia_DrewesJulia Drewes, Ph.D., Post-Doctoral Fellow, Oncology, Johns Hopkins School of Medicine, Bloomberg Kimmel Institute for Immunotherapy

We now understand that the microbiome may be involved in all aspects of colorectal cancer, from protection and prevention, to initiation and progression, and more recently to the response to chemotherapy and immunotherapy. Drawing on studies in both patients and mice, this presentation will discuss recent advances in identifying potential microbial targets and potential pitfalls during immunotherapy.

11:20 Pharmacological Targeting of Gut Microbiota to Improve Anti-Cancer Drug Efficacy

Aadra_BhattAadra Bhatt, Ph.D., Post-Doctoral Fellow, Chemistry, University of North Carolina at Chapel Hill

Irinotecan is an anti-cancer drug that causes gastrointestinal (GI) side effects in 88% of patients. Detoxified irinotecan metabolites are reactivated within the intestinal lumen by microbial ß-glucuronidase (GUS) enzymes, resulting in epithelial cell death and acute diarrhea. Our pre-clinical studies using potent, selective and non-lethal GUS inhibitors reveal diminished GI side effects when administered in conjunction with compounds whose metabolites are reactivated by microbiota.

11:50 Late Breaking Presentation

12:20 pm Sponsored Presentation (Opportunity Available)

12:35 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:05 Session Break

USING THE MICROBIOME TO PREDICT RESPONSE

2:05 Chairperson's Opening Remarks

Wei Zhou, Ph.D., Post-Doctoral Research Associate, The Jackson Laboratory for Genomic Medicine

2:10 High Diversity and Differential Composition of the Gut Microbiome Are Linked to Slower Cancer Progression on Immune Checkpoint Blockade

Vancheswaran_GopalakrishnanVancheswaran Gopalakrishnan, Ph.D., Post-Doctoral Fellow, Surgical Oncology, University of Texas MD Anderson Cancer Center

Recent evidence in murine models suggests that modulation of the gut microbiome may enhance responses to immune checkpoint blockade. We collected oral and gut microbiome samples from melanoma patients initiating treatment with PD-1 blockade (n=112). Responders had a significantly higher alpha diversity (p<0.05), and enrichment of the Ruminococcaceae family compared to non-responders, who had a significant enrichment of Bacteroidales. Immune profiling demonstrated a positive correlation between CD8 density and abundance of bacteria enriched in R.

2:40 Models of Microbial Adjuvants Biomarkers of Cancer Immunotherapy

Wei_ZhouWei Zhou, Ph.D., Post-Doctoral Research Associate, The Jackson Laboratory for Genomic Medicine

Cancer immunotherapies harness the power and specificity of the immune system to attack tumors while sparing normal tissue. However, tumor responses to immunotherapy have been highly variable. Host genetics together with the mutational landscape of the tumor must account for some of this variability, but additional systemic factors are likely to further shape immunotherapeutic efficacy. A nascent body of evidence points to the host microbiome, via immune system interactions, as a modulator of treatment responses. Understanding and manipulating these interactions to improve treatment efficacy could transform outcomes for cancer patients. Thus, great potential lies in systematically identifying and validating these microbial factors, as they can be administered as a dietary probiotic during immunotherapy. We describe an experimental platform to systematically identify probiotic candidates that modulate different aspects of the host immune system based on sequence-based reconstructions of the microbial communities of humanized mouse models. Our longterm goals are to systematically characterize the ability of the human intestinal microbiome to improve immunotherapy outcomes in cancer, and to understand how variability in human gut microbiota affects variability in immune modulation and immunotherapy.

3:10 Investigating the Stool Bacteriome and Response to Immunotherapies in Metastatic Renal Cell Carcinoma (mRCC)

Manuel_MaiaManuel Maia, M.D., Fellow, Medical Oncology, City of Hope

Nivolumab has been approved in the 2nd-line for mRCC based on improvement in overall survival. However, no validated biomarkers exist to predict its activity at this point. Based on preclinical studies showing immunomodulatory effects of the gut microbiome in cancer by both inducing and augmenting the activity of immunotherapies, we are currently studying if any specific stool microbiome composition is predictive of clinical (or lack of) benefit in mRCC patients being treated with nivolumab.

3:40 Refreshment Break in the Exhibit Hall with Poster Viewing

4:15 Problem Solving Roundtable Discussions

Cancer Immunotherapy and the Microbiome – What Does it all Mean?

Moderator: Arpita Maiti, PhD, Senior Director, External Science & Innovation, Inflammation & Immunology and Microbiome, Pfizer Inc.

  • What gaps in the research can be addressed to move the microbiome beyond correlation to causation in cancer and immunotherapy?
  • What technological advances are required (in vitro, ex vivo, and in vivo models, computational tools, ‘omic tools) to gain a true mechanistic understanding of how the functional microbiome interacts with the immune system?
  • What will a microbiome-based therapeutic look like for cancer immunotherapy?
  • Can the microbiome be used to predict treatment response?
  • What will be required to successfully commercialize a microbiome-based therapeutic for oncology?

What is the Future of Microbiome-Cancer Research?

Moderator: Lata Jayaraman, Ph.D., Head, Tumor Immunotherapy, Seres Therapeutics

  • Role of microbiota in modulating host immune response to checkpoint inhibitors - what do we know?
  • Defining the gaps in our current understanding of how the gut microbiota modify the already complex immune response to cancer
  • Strategies to better exploit the tools we have and develop new tools for understanding mechanism of action
  • Drugging the microbiome - can we apply our increasing knowledge in this area to design ecobiotic drugs for combination with checkpoint therapy?

5:15 Welcome Reception in the Exhibit Hall with Poster Viewing

WEDNESDAY, December 6

8:00 am Morning Coffee

MICROBIOME THERAPEUTICS IN IO

8:25 Chairperson's Opening Remarks

Shrish Budree, M.D., Senior Clinical Research Fellow, Clinical Research, Openbiome

8:30 Translational Aspects of Microbial Therapeutics in Immune-Oncology: Current Practices to Future Therapies

Shrish_BurdeeShrish Budree, M.D., Senior Clinical Research Fellow, Clinical Research, Openbiome

There is growing evidence that the intestinal microbiome may enhance the efficacy of checkpoint inhibitors in the treatment of cancer. However, the clinical response to these checkpoint inhibitors is variable among patients, a feature which may be mediated through the gut microbiome. Recent studies in animal models have demonstrated that restoring a healthy intestinal microbiome enhances T-cell infiltration into the tumor microenvironment and augments tumor regression. Mice with a dysbiotic microbial community exhibit a poorer response to checkpoint inhibitors in comparison to their genetically identical counterparts with a healthy microbiome. Co-housing these mice, which is effectively analogous to performing a fecal microbial transplant (FMT), ameliorated this difference in response and enhanced the anti-tumor response in the previously dysbiotic mice. These seminal studies have laid the ground work for future translational studies in patients with malignancies on checkpoint inhibitor, aimed at evaluating the role of FMT in relation to the efficacy of checkpoint inhibitors. This talk will explore the current literature supporting the role of FMT in enhancing the efficacy of checkpoint inhibitors and the possibility of designing future human FMT trials.

9:00 Microbiome Derived Immunotherapies in Cancer

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

Based on its metagenomics platforms, Enterome discovers microbiome-derived molecules acting as specific and unspecific activator of adaptive immune response against tumors. Several candidates are in preclinical development for the treatment of various types of cancer such as glioblastoma, colon, pancreatic, lung and breast.

9:30 Unravelling Microbiome Signatures for Designing Ecobiotics for Combination with Immunotherapies

Lata Jayaraman, Ph.D., Head, Tumor Immunotherapy, Seres Therapeutics

The human gut microbiome is a diverse, dynamic and complex ecosystem that contains many different types of micro-organisms. Gut microbiota modulate several host processes including metabolism, inflammation and immune and cellular responses. Recent studies have shown that the micobiome can also influence the development of cancer, and equally importantly, tumor response to therapy, especially immunotherapy. It is therefore not inconceivable that therapeutic utility of the microbiome to enhance clinical response is a distinct possibility in the not-so-distant future. This presentation will cover the challenges and advantages of developing the microbiome as a drug.

10:00 Sponsored Presentation (Opportunity Available)

10:15 Coffee Break in the Exhibit Hall with Poster Viewing

FUTURE DIRECTIONS

10:45 Cancer Immunotherapy and the Gut Microbiome: A Biomarker or a Probiotic?

Sandip_PatelSandip Patel, M.D., Assistant Professor, Cancer Immunotherapy Program, Experimental Therapeutics, Thoracic Oncology; Assistant Director, Clinical Trials Office, Medicine/Hematology & Oncology, University of California, San Diego Moores Cancer Center

A review of the state of microbiome science and cancer immunotherapy, with a focus on published data correlating gut microbiome to response to immune checkpoint blockade. Novel methods of microbiome assessment for discovery as well as host-immune interactions to develop microbiome signatures to correlate with immunotherapeutic response and toxicity. Overview of novel immunotherapy biomarkers and immunotherapeutic targets, and potential future directions in microbiome science as it pertains to novel cancer immunotherapeutics.

11:15 CLOSING PANEL DISCUSSION: Future Directions in Microbiome Research

Moderator: Arpita Maiti, PhD, Senior Director, External Science & Innovation, Inflammation & Immunology and Microbiome, Pfizer Inc.

  • Microbiome as a biomarker for cancer
  • Microbiome as a predictor of treatment response
  • Beyond oncology, additional roles of the microbiome
  • Commercialization of microbiome therapies

Panelists:

Pranab Mukherjee, MSc, Ph.D., Associate Professor, Dermatology, Case Western Reserve University

Lata Jayaraman, Ph.D., Head, Tumor Immunotherapy, Seres Therapeutics

12:15 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:45 Dessert Break in the Exhibit Hall with Poster Viewing


1:15 PLENARY KEYNOTE SESSION click here for more information 
Manufacturing Chimeric Antigen Receptor T Cells for Early Phase Clinical Trials
David F. Stroncek, M.D., Chief, Cell Therapy Section, Transfusion Medicine, NIH Clinical Center
Evolution of Cancer Immunotherapy
Ramy Ibrahim, M.D., VP, Clinical Development, Parker Institute for Cancer Immunotherapy

2:50 Close of The Microbiome in Cancer Immunotherapy