Preclinical and Translational Immuno-Oncology Icon

Cambridge Healthtech Institute’s Second Annual

Preclinical and Translational Immuno-Oncology

Predictive Preclinical Models for Cancer Immunotherapy
August 29-30, 2017 | Sheraton Boston | Boston, MA


The recent advancements in immunotherapies, such as immune checkpoint modulators, bispecific antibodies, and adoptive T cell transfer, are shifting the way cancer patients are treated. Rapid development of novel immuno-oncology programs is creating the need for predictive preclinical models and translational strategies to understand combination cancer therapy, study responses to cancer immunotherapy, and identify novel biomarkers and targets. Please join Cambridge Healthtech Institute’s Second Annual Preclinical and Translational Immuno-Oncology meeting and learn about new clinically-relevant models for screening IO therapies and translational strategies to support clinical IO programs.



Final Agenda

TUESDAY, AUGUST 29

12:00 pm Registration

TRANSLATIONAL IMMUNO-ONCOLOGY

1:15 Chairperson’s Opening Remarks

Litao Zhang, Ph.D., Vice President, Leads Discovery and Optimization, Bristol-Myers Squibb

1:20 Advances, Challenges and Future of Translational Systems Pharmacology in Cancer Immunotherapy

Sihem_BihorelSihem Bihorel, MS, Pharm.D., Ph.D., Assistant Professor, Department of Pharmaceutics, College of Pharmacy, University of Florida

Two examples of quantitative systems pharmacology will be presented as they represent extremes of a spectrum of modeling complexity. The first example describes a hierarchical modeling approach where a large mechanistic mathematical model provided a framework to integrate a wide variety of experimental data, from in vitro observations to clinical trial results (bottom-up approach in QSP). The second example describes a modeling approach where the mechanistic model is connected to specific experimental data, which are acquired to inform the dynamic quantitative nature of the modeled biological system. Thus, the predictive power of the mechanistic model is more focused on a specific clinical question (top-down approach in QSP).

1:50 Generating Translational Hypotheses to Guide Development of IO Therapies

Laurence_MenardLaurence Menard, Ph.D., Senior Research Investigator, Bristol-Myers Squibb

Response rates to immuno-oncology therapies are still low in some types of cancers or subsets of patients. Thus, it is crucial to understand the immunologic heterogeneity of cancer patients in order to tailor the right medicine to the right patient. We have carried out a prospective immunologic analysis of cancer patients’ tumors and blood to generate testable hypotheses for tumor selection and patient stratification in clinical trials.


2:20 KEYNOTE PRESENTATION: Translation of Cancer Vaccines from Mice to Human Clinical Trials

Jay_BerzofskyJay A. Berzofsky, M.D., Ph.D., Chief, Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health

We translated two cancer vaccine platforms from mice to human clinical trials with promising results: 1) An epitope-enhanced TARP prostate cancer vaccine that induced human T cells that killed human cancer cells. In stage D0 prostate cancer patients, the vaccine reduced PSA slope measuring tumor growth rate in 74% of subjects at 1 yr (p = 0.0004). 2) An adenoviral vector HER2 vaccine cured mice with large established tumors and showed clinical benefit in 45% of evaluable advanced metastatic cancer patients with HER2+ tumors at the 2nd and 3rd dose levels.

MIBioresearch2:50 Methods and Models to Evaluate Preclinical Radiation Treatment Strategies

Maryland Franklin, Ph.D., Vice President, Scientific Development, MI Bioresearch

Radiation treatment is a main-stay in clinical oncology practice. Small animal focal radiation instruments allow radiation and radiation combinations to be utilized in a range of preclinical oncology models. Of particular interest is the possible use of focal radiation to broaden the efficacy and response duration of immuno-oncology therapy.

Nilogen Oncosystems3:05 3D Spheroid Models of Fresh Patient Tumors: Ex vivo Analysis of Immune Microenvironment and Rational Combination Therapy

Soner Altiok, MD, Ph.D., CSO, Nilogen Oncosystems

Nilogen’s 3D-EX℠ platform utilizes fresh patient tumor tissue with intact microenvironment allowing for analysis of the interactions between the immune system and components of cancer tissue. We can accurately assess efficacy, identify rational combinations and develop companion diagnostics for biomarker-driven drug development and personalized medicine reducing both the cost and risk.

3:20 Refreshment Break in the Exhibit Hall with Poster Viewing


4:00 PLENARY KEYNOTE SESSION

4:00 Regulatory and Scientific Considerations for Cancer Vaccines and Adoptive Cellular Immunotherapy

Raj Puri, M.D., Ph.D., Division Director, Center for Biologics Evaluation and Research, FDA

Cell and Gene therapy including therapeutic vaccines and cellular immunotherapy products are evaluated at FDA’s Center for Biologics Evaluation and Research in the Office of Tissues and Advanced Therapies (OTAT) previously known as Office of Cellular, Tissue and Gene Therapies. I will discuss current general regulatory and scientific considerations in the regulation of therapeutic cancer vaccines and cellular immunotherapy. In addition, research activities in OTAT will be summarized.

4:45 Market Access and Reimbursement for Immuno-Oncology Drugs in Today’s Healthcare System

Gergana Zlateva, Ph.D., Vice President, Payer Insights and Access, Oncology, Pfizer

Now that immunotherapies have hit the market, with the promise of more to come, the healthcare system will need to establish standards for cost and reimbursement of immuno-oncology agents. This talk will address how the healthcare marketplace can prepare for the adoption of novel pricing and reimbursement models to increase patient access to immunotherapies. Establishing the value of IO therapies to payers and HTAs will also be addressed in the context of pricing and evidence generation.

Click here for keynote biographies

5:30 Welcome Reception in the Exhibit Hall with Poster Viewing

5:30 Dinner Short Course Registration*

SC1: Bioinformatics for Immuno-Oncology and Translational Research

SC2: Microbiome in Immuno-Oncology

*Separate registration required, please click here for more information.

WEDNESDAY, AUGUST 30

7:00 am Registration

7:25 Breakout Discussion Groups with Continental Breakfast

PRECLINICAL MODELS FOR IMMUNOTHERAPY DEVELOPMENT

8:25 Chairperson’s Remarks

Litao Zhang, Ph.D., Vice President, Leads Discovery and Optimization, Bristol-Myers Squibb

8:30 Using Mouse Models to Understand Tumor Genotypes in Shaping Up Tumor Microenvironment

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

Tumor microenvironment plays a critical role in anti-tumor immune response. We are interested in the correlation between tumor microenvironment and a number of tumor cell autonomous properties, including key genetic alterations, tissue origins and tumor locations. By using appropriate animal models derived from isogenic cancer progenitors that represent different tissue origin, we are able to make some detailed comparisons.

9:00 Developing Humanized Mouse Models to Evaluate Antitumor Efficacy and Mechanism of Action in Cancer Immunotherapy Studies

Carmine Carpenito, Ph.D., Principal Scientist, ImClone Systems, Eli Lilly & Co.

Immunodeficient mice permit the engraftment of human tumor and immune cells. These humanized xenograft models provide powerful tools to interrogate biological effects of human-specific immunomodulatory agents and provide important insights into their mechanism of action. We will describe different models and how they can be used to facilitate drug development in immuno-oncology.

9:30 Humanized Mouse Models for Preclinical Testing of Immune Checkpoint Modulators

Ella_IoffeElla Ioffe, Ph.D., Associate Director, Immune-Oncology, Regeneron Pharmaceuticals

Immune checkpoint receptors promote cancer immune tolerance by suppressing effector T cell activity. The development of immune checkpoint inhibitors has revolutionized cancer treatment. However, clinical antibodies against checkpoint receptors typically do not recognize murine proteins. Therefore, we developed mouse models where the therapeutic targets have been humanized using genetic engineering or reconstitution with primary human cells. These humanized models allow preclinical in vivo testing of fully human Regeneron antibodies.

TD2 tagline10:00 Animal Models That Focus on Adaptive and Innate Immunity to Improve the Activity of Immunotherapies

Paul Gonzales, Vice President, Non-Clinical Operations, TD2

TD2 will present T512 data on T and NK cytotoxicity screening, flow on T/NK cell movement, and flow for NK ligands.

DiscoverX10:15 Human Tumor Microenvironment Models Support Evaluation and Prioritization of Combination Strategies for Immuno-Oncology

Alison O’Mahony, Ph.D., Vice President, Research Biology, DiscoverX Corporation

Combination and bi-specific therapies frequently achieve greater clinical benefit, however prioritizing these approaches over monotherapies can be challenging pre-clinically. BioMAP® human tumor-microenvironment models provide an evidence-based approach to qualify and guide these therapies via identification of differential IO-related immune activities, effects on TME and determining optimal exposures towards enhanced efficacy.

10:30 Coffee Break in the Exhibit Hall with Poster Viewing

11:15 Evaluating Anti-Tumor Immune Responses in Preclinical Mouse Models

Marcus Bosenberg, M.D., Ph.D., Associate Professor, Dermatology and Pathology, Yale School of Medicine; Co-Leader, Genomics, Genetics and Epigenetics Program, Yale Cancer Center

Identification of autoimmune phenotypes in mice led to the development of anti-CTLA-4 and PD-1 drugs. While this approach has been very successful, there is great interest in overcoming resistance to checkpoint inhibitor therapy and in improving responses in cancers with low response rates. Testing of new immune therapeutic approaches in cancer requires models that accurately reflect responses in humans and allow for in-depth evaluation of mechanism of action.


11:45 KEYNOTE PRESENTATION: Accelerating Immuno-Oncology Drug Candidate Selection and Optimization: Dissecting Cancer Immunity Cycle through Quantitative and Advanced Immune Assay Technology Platforms

Litao Zhang, Ph.D., Vice President, Leads Discovery and Optimization, Bristol-Myers Squibb

Cancer immunity in nature requires the coordination of both immune stimulatory and inhibitory signaling mechanisms that occur in the tumor microenvironment. In this talk, we will share how to select right translational models to quantitatively monitor and characterize IO therapeutic agents. 3D bioprinting technology, co-culture systems and CRISPR will be used to model and mimic tumor microenvironment. Through these advanced technology platforms, biomarker profiling strategy will be discussed. The challenges and solutions to close the gaps in the IO drug discovery will be shared.

12:15 pm Profiling Protein Signaling and Functional Response of Checkpoint Inhibitor and Combination Treatments in Patient-Derived Tumor Immune Cell Co-Culture Models

Christophe_SachseChristophe Sachse, Ph.D., Site Head Berlin, NMI TT Pharmaservices

We have established an ever-growing panel of primary patient-derived 3D co-culture models of tumor spheroids and T lymphocytes, which we employ in high-content assays for the evaluation of lymphocyte infiltration and T cell induced cytotoxic effects during in vitro drug testing. Also, our 3D models are analyzed by comprehensive DigiWest-based phospho-protein profiling of several transduction pathways, which yields in-depth data on cell signaling and adds considerable value beyond genomics analyses.

Charles River Discovery12:45 Luncheon Presentation: Advances in Immune-Checkpoint Inhibitors Therapies for the Treatment of Solid Tumors in Humanized Mouse Models

Paula Miliani de Marval, Ph.D., Research Associate Director, Charles River

The need for more relevant preclinical models has led us to evaluate the antitumor efficacy of anti-CTLA-4 and anti-PD-1 checkpoint inhibitors in CD34+ and PBMC humanized mouse models. The findings of these studies will be discussed, along with the advantages and disadvantages of each model.

1:15 Session Break

TARGETING THE TUMOR MICROENVIRONMENT: ACTIVATING THE IMMUNE SYSTEM FOR BETTER RESPONSE TO IMMUNOTHERAPY

1:55 Chairperson’s Remarks

Pawel Kalinski, M.D., Ph.D., Professor, Oncology, Vice-Chair, Translational Research, Roswell Park Cancer Institute

2:00 Combinatorial Modulation of “Cold” Tumors to Promote Selective CTL Entry: Sensitization to PD-1/PD-L1 Blockers and Vaccines

Pawel_KalinskiPawel Kalinski, M.D., Ph.D., Professor, Oncology, Vice-Chair, Translational Research, Roswell Park Cancer Institute

Presence of CTLs in tumor lesions predicts improved outcomes and patients’ responsiveness to checkpoint blockers. Combinatorial approaches, in contrast to mono-adjuvants, allow two levels of selectivity: 1) preferential activation of tumor microenvironments, rather than healthy tissues; 2) selective intratumoral induction of CTL-attracting chemokines, but suppression of Treg-attractants. Data from preclinical studies (ex vivo tissue explant cultures and mouse tumor models) and early-stage clinical trials will be discussed.

2:30 Intratumoral Immunotherapy: Overcoming Immune Resistance and Activating the Adaptive and Innate Immune Responses

Adi_DiabAdi Diab, M.D., Assistant Professor, Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center

3:00 Sponsored Presentation (Opportunity Available)

3:30 Refreshment Break in the Exhibit Hall with Poster Viewing

4:15 Clinical Cancer Immunotherapeutic Approaches Utilizing STING-Activating Cyclic Dinucleotides and Live-Attenuated Listeria-Based Platforms to Target Tumor-Specific Neoantigens

Sarah_McWhirterSarah McWhirter, Ph.D., Director, STING Program, Aduro Biotech

Interventional strategies that combine tumor microenvironment (TME) remodeling with lymphocyte infiltration, induction of tumor-specific cellular immunity and blockade of immune checkpoint pathways can result in effective and durable anti-tumor efficacy. We have developed two clinical approaches, based on small molecule STING agonists and live-attenuated double-deleted Listeria monocytogenes (LADD) that accomplish these therapeutic goals. Preclinical and clinical immunotherapeutic regimens combining STING agonists and pLADD with immune checkpoint inhibitors will be discussed.

4:45 Using Radiation to Elicit in situ Tumor Vaccination

Zachary_MorrisZachary S. Morris, M.D., Ph.D., Assistant Professor, Human Oncology, University of Wisconsin School of Medicine and Public Health

In a syngeneic murine melanoma model, we recently reported an in situ vaccination response to combined radiation (RT) and intra-tumor (IT) injection of anti-GD2 hu14.18-IL2 immunocytokine (IC). This combined treatment resulted in 71% complete and durable regression of 5-week (~ 200mm3) tumors, a memory T cell response, and augmented response to systemic anti-CTLA-4 antibody (mAb) checkpoint blockade. We hypothesized that mice rendered disease-free (DF) by combined RT, IT-IC, and anti-CTLA-4 mAb might also exhibit an anti-tumor endogenous humoral response. Here we report an endogenous anti-tumor memory IgG humoral response in mice > 1 year after treatment with RT IT-IC and anti-CTLA-4 mAb. We demonstrate the emergence of this endogenous humoral response in the weeks following treatment and explore mechanisms whereby this response may contribute to the therapeutic efficacy and immunologic memory elicited by this in situ vaccination regimen.

5:00 The Role of Batf-3 DC in the T Cell-Inflamed Tumor Microenvironment

Stefani_SprangerStefani Spranger, Ph.D., Assistant Professor, Biology, MIT

Immunotherapy has revolutionized the treatment of cancer, and while the number of cancers with responses towards immunotherapies is still growing, it has also been observed that only a fraction of patients is responding within each cancer type. We investigated whether tumor cell-intrinsic signaling might dominantly impact local T cell infiltration and identified that patients with activated β-catenin signaling lack a productive anti-tumor T cell infiltrate. Mechanistically, we identified that β-catenin-positive tumors fail to recruit Batf3-driven dendritic cells into the tumor microenvironment. Detailed studies have identified that these dendritic cells are not only needed to activate anti-tumor specific T cells in the tumor-draining lymph node but are also required within the tumor microenvironment as the predominant source of effector T cell recruiting chemokines.

5:15 Vaccine Therapy for Primary and Secondary Breast Cancer Prevention

Sasha_StantonSasha Stanton, M.D., Ph.D., Acting Instructor, Breast Oncology, University of Washington Tumor Vaccine Group

Vaccine therapy may both destroy ductal carcinoma in situ (DCIS) and prevent progression to invasive breast cancer (IBC). We have identified DCIS tumor associated proteins that are essential for breast cancer survival and immunogenic in DCIS. Furthermore, bexarotene, a rexinoic acid receptor agonist, can activate type 1 antigen presenting cells and induce a type 1 tumor immune environment. We are developing a multi-antigen polyepitope DCIS vaccine to determine if addition of bexarotene can improve vaccine efficacy.

5:30 Combining Targeted Radiation with Immunotherapy

Jonathan_SchoenfeldJonathan D. Schoenfeld, M.D., MPhil, MPH, Assistant Professor, Radiation Oncology, Harvard Medical School

Preclinical data suggests targeted radiotherapy has immune stimulating effects that may increase the efficacy of immunotherapy. However, radiotherapy also has immune suppressive effects. In this session, we will review data that suggests that radiation may be a good partner for immunotherapy, and the types of radiation that are best suited for this purpose. We will also discuss emerging clinical data supporting the combination and ongoing and planned clinical trials.

6:00 Close of Preclinical and Translational Immuno-Oncology


Japan-Flag Korea-Flag China-Simplified-Flag China-Traditional-Flag

Register Today
Celebrating 25 Years



2017 Download Brochure


IPR_IMX_Banner