Cambridge Healthtech Cambridge Healthtech Institute’s Inaugural

Targeting the Tumor Microenvironment

Improving Immunotherapy Outcomes through Deeper Understanding of the TME

December 6-7, 2017 | Hilton San Diego Resort | San Diego, CA

With record numbers of immunotherapies in active development, the importance of the tumor microenvironment (TME) in creating, tailoring, and monitoring therapies has become clear. Cambridge Healthtech Institute’s Inaugural Targeting the Tumor Microenvironment will address three critical components of the role of the tumor microenvironment in immunotherapy. First, the biology and composition of the TME will be examined to understand the function and presence of different immune cells. Then, the role of the TME in therapy prediction and monitoring will be addressed, with specific focus on immunoscoring. Finally, strategies for targeting cellular and molecular components of the TME will be discussed.

Final Agenda

WEDNESDAY, December 6

12:00 pm Conference Registration

12:15 A Novel Phenotypic Approach for Predicting Tumor Response

Mark_ParisMark Paris, Ph.D., Associate Director, Translational Applications, Mitra Biotech

Mitra Biotech has developed and clinically validated our fully human ex-vivo platform technology (CANscript™)
. CANscript ™ uses patient material (tumor, autologous ligands and PBMC) to explore the mechanism of action and predict efficacy for clinically-directed compounds in a modality-agnostic way using phenotypic effects.
 This talk will explore the effects of anti-PD1 on CANscript tumor culture as insight into the capabilities of the platform.

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 Refreshment Break in the Exhibit Hall with Poster Viewing


3:30 Chairperson's Opening Remarks

Zhao Chen, Ph.D., Investigator III, Exploratory Immuno-Oncology, Novartis Institute of Biomedical Research

3:35 KEYNOTE PRESENTATION: Solving the 'Last Mile Problem': Delivering Oxygen Deep into Hypoxic Tumor Microenvironments

Cary stephenStephen Cary, Ph.D., Co-Founder & CEO, Omniox

The hypoxic tumor microenvironment promotes immune tolerance by altering the recruitment and function of innate and adaptive immune effector and suppressor cells. Reversing tumor hypoxia provides an attractive combinatorial approach to improve immunotherapy response in solid tumors. To date, there have been no effective approaches to target tumor hypoxia, and in particular to specifically re-oxygenate the hypoxic microenvironment to restore more normal tissue biology. We engineered a very high affinity oxygen carrier, OMX-4.80P (OMX), to accumulate preferentially in tumors through the enhanced permeability and retention (EPR) effect, and to release oxygen only in the presence of severe hypoxia. By delivering oxygen specifically to the hypoxic tumor microenvironment, OMX restores anti-cancer immune responses and synergizes with immunotherapies to enhance tumor control and cures.

4:05 Genotype, Tissue Type and Tumor Microenvironment

Zhao Chen, Ph.D., Investigator III, Exploratory Immuno-Oncology, Novartis Institute of Biomedical Research

Cancer cells play key roles in shaping up the tumor microenvironment. Cancer genetic studies also tell us that much of the behavior of the tumor is dictated by genetic alterations and tissue origin. However, the link is missing between these tumor cell autonomous traits and their corresponding influence on tumor microenvironment. We are interested in charactering genotype and tissue type dependency of tumor microenvironment, and its relevance to treatment responses.

4:35 Oncogenes: Regulators of Immune Privilege

Dean_FelsherDean W. Felsher, M.D., Ph.D., Director, Translational Research and Applied Medicine, Oncology Research, Stanford University School of Medicine

We have shown that many oncogenes induce tumorigenesis that is completely reversible upon their inactivation, a phenomenon called oncogene addiction. Recently, we have found that oncogenes causally regulate the expression of key immune checkpoints including PD-L1 and CD47. Therapies that target specific oncogenic pathways can restore the immune response against cancers. Our observations have important implications for how therapies that target oncogenes can restore the immune system against cancers.

5:05 Close of Day

THURSDAY, December 7

8:00 am Breakfast Breakout Roundtable Discussions

Targeting Immune Suppression

Moderator: Elizabeth Evans, Ph.D., Vice President, Preclinical Research, Vaccinex

  • Beyond Treg, what types of immunosuppressive cells and signals are thought to be the most promising new targets?
  • Key markers and functional assays to characterize myeloid cells in TME, human and mouse
  • Key markers and functional assays to characterize myeloid cells in TME, human and mouse.
  • What are critical biomarkers to assess immunosuppression? Where and how can these be assessed – liquid biopsies, tumor tissue, lymph nodes?

Immune Cell Targets in the Tumor Microenvironment

Moderator: David Wustrow Ph.D., Vice President, Drug Discovery FLX Bio

  • Key targets immune cell migration and function in the TME
  • Pathways and targets in the adaptive immune system
  • Pathways and targets in the innate immune system
  • Identifying synergistic combinations with existing therapeutic modalities


8:55 Chairperson's Opening Remarks

David Wustrow, Vice President, Drug Discovery, FLX Bio, Inc.

9:00 Small Molecule Approaches to Reversing Immunosuppression in the Tumor Microenvironment by Inhibiting Regulatory T Cells

David_WustrowDavid Wustrow, Vice President, Drug Discovery, FLX Bio, Inc.

Mechanistic studies have revealed that regulatory T cells (Treg) play a key role in suppressing immunity in the tumor microenvironment. Small molecule Treg targets that either reduce Treg numbers in the tumor or their suppressive function have been identified. The selectivity, titratability and access of small molecules to intracellular compartments provide differentiation with biologics and allow novel combinations with approved IO agents to increase response rates in established therapies as well as establishing efficacy across a broader variety of tumor types. This talk will discuss progress in identification and development of small molecules that can effectively enhance the immune response in the tumor microenvironment by inhibiting the suppressive effects of Treg on CD8+ effector T cells.

9:30 Next generation Biomarkers for the Era of Combination Cancer Immunotherapies

Sarah Javaid, Ph.D., Senior Scientist, Discovery Pharmacogenomics, Genetics, Pharmacogenomics, Merck

Immune checkpoint blockade therapies are revolutionizing the standard cancer treatment. Despite the current success of these therapies, not all patients respond to immunotherapy and even those that do often experience toxicities. Combination approaches are the keys to improving clinical response. Novel high throughput technologies enable us to understand the mechanisms underlying the complex interactions between the immune system and cancer and identify predictive biomarkers for patients.

10:00 Tapping Into CAR T Cell Associated TME Gene Signature to Optimize Immunotherapy

Adrian Bot, M.D., Ph.D., Vice President, Translational Sciences, Kite Pharma

Chimeric antigen receptor (CAR) engineered T cells have shown promising clinical efficacy and manageable toxicities in multicenter clinical trials, and are entering clinical practice. Clinical activity of CAR T cells has been previously associated with a range of blood biomarkers. Complementing this extensive analysis of blood markers, a detailed evaluation of CAR T cell treatment related TME changes is needed. Recently, utilizing nanostring applied to tumor biopsies pre-and 7-14 days post CAR T cell treatment, we identified a TME gene signature related to CAR T cell treatment. Emerging results from our study suggest that optimizing the CAR T cell proliferative capability by exploiting IL-15, in conjunction with modulation of interferon related pathways and TME checkpoints, could result in more efficacious T cell interventions.

10:30 Networking Coffee Break

10:55 Targeting the Tumor Immunoenvironment

Michael_ShurinMichael R. Shurin, M.D., Ph.D., Professor, Pathology, Immunology, University of Pittsburgh Medical Center

Targeting immune regulatory cells in cancer has been proven as an effective monotherapy or a part of combinational cancer treatment. However, cancer chemoresistance is still the main reason for therapeutic failure. Our new data provide a new role of myeloid regulatory cells in chemoresistance and offer a novel nanodelivery approach to cell specific targeting of these cells in the tumor microenvironment. In addition, our new data suggest that targeting the peripheral nervous system in cancer may alter the tumor immunoenvironment and potentially control tumor progression.


11:25 First-in-Class Anti-Semaphorin 4D Antibody Shifts the Immune Balance in the Tumor Microenvironment

Elizabeth_EvansElizabeth Evans, Ph.D., Vice President, Preclinical Research, Vaccinex

Semaphorin 4D (SEMA4D) is highly expressed at invasive tumor margins, where it promotes immune suppression in the tumor microenvironment by restricting immune cell infiltration and activity. Preclinical mechanistic studies demonstrate that neutralizing anti-SEMA4D antibodies can restore the immune balance and inhibit tumor growth. Anti-SEMA4D antibody treatment synergizes with other immunomodulatory agents to enhance anti-tumor responses, supporting the initiation of Phase Ib/II studies of anti-SEMA4D in combination with immune checkpoint therapies.

11:55 USP7 Modulating Tumor Microenvironment with USP7 Inhibitors for Cancer Immunotherapy

Suresh_KumarSuresh Kumar, Ph.D., Senior Director, R&D, Progenra, Inc.

Immune suppressive Tregs in the tumor microenvironment correlate with poor prognosis. Depletion of Tregs or impairment of Treg function is an attractive cancer immunotherapy approach. USP7 controls Treg function by regulating Foxp3 and TIP60. Progenra has developed potent USP7 inhibitors that impair Treg functions and are efficacious in various syngeneic solid tumor models. USP7 inhibitors alone or in combination can improve the efficacy and expand the scope of cancer immunotherapy.

12:25 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:55 Session Break


1:55 Chairperson's Opening Remarks

Osama Rahma, M.D., Assistant Professor, Medicine, Center for Immuno-Oncology, Gastrointestinal Cancer Center, Dana-Farber Cancer Institute, Harvard Medical School

2:00 Utilizing the Neoadjuvant Immunotherapy Setting for a Better Understanding of the Tumor Microenvironment

Osama_RahmaOsama Rahma, M.D., Assistant Professor, Medicine, Center for Immuno-Oncology, Gastrointestinal Cancer Center, Dana-Farber Cancer Institute, Harvard Medical School

Despite the recent progress in cancer immunotherapy drugs development questions regarding their mechanism of action and resistance still exist. Many answers lay in the tumor microenvironment (TME) that may not be always accessible. Accordingly, neoadjuvant immunotherapy provides a perfect setting to test the effect of these agents. We will discuss the currently ongoing trials utilizing neoadjuvant immunotherapy to better understand the TME.

2:30 Gene Signatures and Cellular Architect Needed for Boosting Anti-Tumor Immunological Therapies

Sanjay Khare, Ph.D., President, ImmunGene

3:00 Networking Refreshment Break


3:15 Evaluation of Immune Cell Infiltrates in the Tumor Microenvironment Using Multiplex Immunohistochemistry

Shawn_JensenShawn Jensen, Ph.D., Senior Scientist, Molecular and Tumor Immunology, Robert W Franz Cancer Research Center, Earle A Chiles Research Institute, Portland Providence Medical Center

The assessment of T cell infiltrates in the tumor microenvironment using immunohistochemistry has been shown to be a powerful prognostic biomarker in some cancers. Next generation “immunoscore” of the tumor microenvironment using multiplex immunohistochemistry imaging enables analysis of multiple cell phenotypes as well as their spatial relationships. Data from this analysis can improve prognosis of cancer patients as well as inform us on future targets for immunotherapy.

3:45 Integrated Immunotherapy Based upon Tumor/Host interaction

Alan_EpsteinAlan L. Epstein, M.D., Ph.D., Professor, Pathology, Keck School of Medicine, University of Southern California

Cancer immunotherapy is beginning to enter the clinic as a key therapeutic approach to supplement existing treatments. However, a better understanding of the tumor/host interaction would enable clinicians to customize immunotherapy for optimal effects. For this to occur, specific elements of this interaction need to be identified at the time of diagnosis including HLA status, presence of immune cells and co-stimulation in the tumor mass or surroundings, and the identification of dominant immunosuppressor cells and molecules. Using murine syngeneic tumors as models, we have identified these parameters to customize immunotherapeutic approaches and shown that addressing immune activation and suppression specifically for each tumor model will enable effective immunotherapy to be applied. In addition to suppressing tumor growth, effective immunotherapy can induce a memory response which is required for preventing resurgence of tumor after cessation of therapy. The importance of biomarkers for the above parameters is as important as the therapy since they will direct proper treatment and help to monitor tumor growth/regression. Our data show that a small number of dominant features of immune activation and inhibition present in the tumor microenvironment need to be addressed to enable immunotherapy to become a potentially curative treatment for cancer regardless of its origin or tumor type

4:15 CLOSING PANEL DISCUSSION: Future Directions in Tumor Microenvironment Research

Moderator: Osama Rahma, M.D., Assistant Professor, Medicine, Center for Immuno-Oncology, Gastrointestinal Cancer Center, Dana-Farber Cancer Institute, Harvard Medical School

  • Challenges moving forward
  • Target validation and identification
  • Modulating the TME to make it less immunosuppressive
  • Surface markers that define the TME
  • Exploring TME mechanisms
  • Getting to and designing clinical trials

Panelists: Zhao Chen, Ph.D., Investigator III, Exploratory Immuno-Oncology, Novartis Institute of Biomedical Research

Elizabeth Evans, Ph.D., Vice President, Preclinical Research, Vaccinex

Michael R. Shurin, M.D., Ph.D., Professor, Pathology, Immunology, University of Pittsburgh Medical Center

4:45 Close of Targeting the Tumor Microenvironment