Cambridge Healthtech Institute　제1회

Targeting the Tumor Microenvironment
(종양 미세환경의 표적화)

종양 미세환경에 관한 연구의 진전에 따른 면역치료의 결과 개선

2017년 12월 6 - 7일 | Hilton San Diego Resort | 캘리포니아주 샌디에고

최근 기록적인 수의 면역치료제 개발이 진행되는 가운데 치료법의 개발 및 조정, 모니터링 시행에서 종양 미세환경(TME)의 중요성이 명확해지고 있습니다. 종양 미세환경의 표적화를 테마로 한 이 컨퍼런스 프로그램에서는 면역치료에서 TME가 담당하는 역할에 주목하면서 3가지 중요 요소에 대해 생각합니다. 또한 생물학과 TME의 구성에 초점을 맞추며 각종 면역 세포의 기능과 존재에 대해 이해하고, immunoscoring에 주목하면서 치료 결과의 예측과 모니터링에서 TME가 담당하는 역할에 대해 검토하고, 마지막으로 TME의 세포 성분과 분자 성분을 표적화하기 위한 전략에 대해 논의합니다.

Final Agenda

Day 1 | Day 2

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

WEDNESDAY, December 6

12:00 pm Conference Registration

12:15 Luncheon Presentation to be Announced

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

UNDERSTANDING THE FUNCTION OF IMMUNE CELLS IN THE TME

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 stephen Stephen 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_Felsher Dean 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 Tapping Into CAR T Cell Associated TME Gene Signature to Optimize Immunotherapy

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

5:35 Close of Day

Day 1 | Day 2

THURSDAY, December 7

8:00 am Breakfast Breakout Roundtable Discussions

UNDERSTANDING THE FUNCTION OF IMMUNE CELLS IN THE TME (CONT.)

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

Mechanistic studies have revealed that regulatory T cells (T_reg) play a key role in suppressing immunity in the tumor microenvironment. Small molecule T_reg targets that either reduce T_reg 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 T_reg on CD8+ effector T cells.

9:30 Ex vivo Preclinical Models for Biomarker Discovery and Translational Research

Svetlana Sadekova, Ph.D., Senior Principal Scientist, Head of Translational Pathology Group, Merck

Rapid advancement of immuno-oncology is creating the need for translational strategies to guide indication selection, understand mechanisms of resistance and identify biomarkers of response. This talk will highlight the importance of understanding human tumor microenvironment and focus on strategies based on utilizing human tissues for pre-clinical and clinical translational research.

10:00 Sponsored Presentation (Opportunity Available)

10:30 Networking Coffee Break

10:55 Targeting the Tumor Immunoenvironment

Michael_Shurin Michael 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.

TARGET VALIDATION AND PRIORITIZATION

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

Elizabeth_Evans Elizabeth 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_Kumar Suresh 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

DRUG DELIVERY STRATEGIES

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_Rahma Osama 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

IMMUNOSCORING AND OTHER PROGNOSTIC TESTS

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

Shawn_Jensen Shawn 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_Epstein Alan 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