Cancer Immunotherapy

Immuno-oncology research and the subsequent development of immunotherapies continue to rapidly advance the fight against cancer. First-generation agents achieving remarkable clinical success have inspired researchers to pursue a variety of new treatment modalities, creating a robust development landscape now centered on combinations strategies. These next-generation agents, in combination with targeted therapies or other immune-modulators such as checkpoint antibodies, are poised to significantly enhance clinical response in a wider range of cancers, and particularly solid tumors.

Cambridge Healthtech Institute’s Third Annual Cancer Immunotherapy meeting is designed to convene an interdisciplinary collection of cancer researchers, drug developers, and technology providers to discuss current challenges and opportunities from discovery biology to clinical studies; share the latest technologies and engineering approaches enabling immunotherapy development; discuss advances in cancer immunotherapy approaches and combination strategies; as well as to provide updates on clinical findings.

Monday, February 12

10:30 am Conference Program Registration Open

TRANSLATIONAL STRATEGIES FOR COMBINATION THERAPY

11:50 Chairperson’s Opening Remarks

James Smothers, Ph.D., Vice President, DPU Head, Immuno-Oncology & Combinations DPU, Oncology R&D, GlaxoSmithKline

12:00 pm Non-Clinical Approaches to Predict Single Agent vs. Combination Value and Clinical Development Strategies for Emerging Cancer Immunotherapies

James Smothers, Ph.D., Vice President, DPU Head, Immuno-Oncology & Combinations DPU, Oncology R&D, GlaxoSmithKline

Non-clinical research studies historically support preclinical development and regulatory submission satisfaction and provide critical support of early clinical development hypotheses and clinical trial design including managing expectations of single agent efficacy or setting strategic vision for combination value through biology synergies. Moreover, following early clinical development milestones, an experimental medicine requires ongoing translational review of the clinical readouts beyond efficacy which in turn requires additional non-clinical analyses and experimental execution to drive results-based decision making and data-informed design of late stage clinical trials in anticipation and hope of drug approvals. Examples of non-clinical studies to support all of these activities will be reviewed including choice of experimental models and design.

12:30 Drivers, Passengers, and Checkpoints: Biomarker Development for Novel Oncology Immuno-Therapies

Nicholas C. Dracopoli, Ph.D.,Senior Vice President, Translational Science, Personal Genome Diagnostics

The majority of novel oncology drugs are still approved without a companion diagnostic even though the probability of regulatory approval is much higher for drugs developed with a diagnostic biomarker. This presentation will review the development of companion diagnostics for novel immuno-oncology drugs and describe strategies to release a prior, but suppressed, immune response to a tumor, or to prime a new response in patients with no prior immune response.

1:00 Session Break

1:10 Luncheon Presentation I: The Current and Future Landscape of Combinational immuno-Oncology Targets

Matthew E. Wampole, Ph.D., Manager, Solution Scientists, Clarivate Analytics

Ongoing challenges for cancer immunotherapies are resistance and lack of efficacy with current treatments. The tumor microenvironment and infiltrating immune cells play an important role in the response to treatment. Combinational therapies are being rigorously tested to overcome these challenges, but additional targets are needed. This presentation will review the current landscape of combinational immuno-oncology therapies and discuss strategies for identifying new combinations.

1:40 Luncheon Presentation II: Overcoming Technology Limitations in Molecular and Cellular Workflows. Case: Standardizing Cell Therapy Workflows

Winny Tan, Ph.D., Strategic Partnerships Manager, imec

A major hurdle to scale up the market of cell therapies is the cost and complexity of the workflow. We propose a novel approach based on a standardised workflow which will be easy to use, reliable and reproducible. Using Silicon chip technology, fully integrated solutions can be built, combining microfluidics, photonics based biosensors, PCR, and single cell manipulation. We will present a portfolio of technologies which will be the building blocks for bioprocessing and delivery of future personalised therapies.

2:10 Session Break

TACKLING THE TUMOR MICROENVIRONMENT:
TARGETING TAMs, MDSCs AND A2A PATHWAY

2:30 Chairperson’s Remarks

Carola Ries, Ph.D., Head, Cancer Immunotherapy I, Pharma Research and Early Development (pRED), Roche Innovation Center Munich

2:40 Macrophage-Targeted Cancer Immunotherapy

Carola Ries, Ph.D., Head, Cancer Immunotherapy I, Pharma Research and Early Development (pRED), Roche Innovation Center Munich

To therapeutically target TAMs, we harnessed their dependence on the key survival factor, macrophage colony-stimulating factor 1 (CSF1), and developed a monoclonal antibody (Emactuzumab/RG7155) that blocks dimerization and activation of human CSF1R. Treatment of cancer patients with Emactuzumab substantially reduces the intratumoral TAM infiltrate. We will present data on a cancer immunotherapy combination, which targets TAMs and stimulates an anti-tumoral T cell response leading to tumor remission in preclinical mouse models.

3:10 Cancer Immunotherapy: Science Driving Combinatorial Strategies

Andy Blake-Haskins, Ph.D., Immuno-Oncology Asset/Team Lead, Pfizer

Most tumors are either inherently resistant to, or will adapt to become resistant to, checkpoint inhibitors. Our challenge is to combine immunotherapy rationally with standard treatment regimens to increase responses or to prevent resistance. Our strategies for combinatorial approaches are: eliciting immunogenic cell death with cytotoxic or radiotherapy, combining anti-angiogenic and targeted therapies with immunotherapy, sustaining responses with immune agonists, inhibiting an immune suppressive microenvironment, and combining immunotherapy with DNA damage response inhibitor.

3:40 EP4 Antagonism in Combination Immuno-Oncology Therapeutic Approaches

Xingfeng Bao, Ph.D., Head, Immuno-Oncology, Integrated Biology Engine, Eisai AiM Institute, Eisai, Inc.

PGE2 in the tumor microenvironment contributes to the accumulation of immunosuppressive myeloid cells by interacting with the EP4 receptor on newly arriving monocytes, skewing their development into MDSCs and TAMs. The EP4 antagonist E7046, now in Phase I/Ib trials, inhibits this interaction and enhances formation of a more favorable anti-tumor immune milieu. This approach combines well preclinically with T cell-directed immunotherapies such as checkpoint inhibitors in boosting anti-tumor immunity.

4:10 EOS100850, an Insurmountable and Non-Brain Penetrant A[2A] Receptor Antagonist, Inhibits Adenosine-Mediated T Cell Suppression and Exhibits Anti-Tumor Activity

Gregory Driessens, Ph.D., Head, In Vivo Pharmacology, iTeos Therapeutics SA

4:40 Refreshment Break and Transition to Plenary Session

5:00 Plenary Keynote Session (click here for more details)

 

Precision for Medicine

 6:00 Grand Opening Reception in the Exhibit Hall with Poster Viewing

7:30 Close of Day

Tuesday, February 13

7:30 am Registration Open and Morning Coffee

8:00 Plenary Keynote Session (click here for more details)

9:00 Refreshment Break in the Exhibit Hall with Poster Viewing

SMALL MOLECULE - CHECKPOINT COMBINATION STUDIES

10:05 Chairperson’s Remarks

Peggy Scherle, Ph.D., Vice President, Preclinical Pharmacology, Incyte Corporation

10:15 Combined Inhibition of IDO1 and PD-1 as an Effective Therapeutic Strategy in Cancer

Peggy Scherle, Ph.D., Vice President, Preclinical Pharmacology, Incyte Corporation

Antibodies to checkpoint receptors have demonstrated unprecedented efficacy in a broad range of tumor types and represent a new paradigm in cancer treatment focused on inhibition of mechanisms that suppress anti-tumoral immunity. Indoleamine-2,3-dioxygenase-1 (IDO1) has also emerged as an immunotherapy target due to its role in regulating T-cell responses. Preclinical and early clinical data will be described that support the combination of IDO1 inhibition with antibodies to checkpoint receptors.

10:45 Selected Poster Presentation: Early Hallmark for Tumor-Induced Dysfunctional Sentinel Lymph Nodes in Breast Cancers

Ting-Fang He, Staff Research Scientist, Immuno Oncology, City of Hope Comprehensive Cancer Center

11:15 Immunologic Effects of Clinical Stage FAK and PI3K-Delta/Gamma Inhibitors

Jonathan Pachter, Ph.D., CSO, Translational Research, Verastem

The efficacy and long term survival observed with our FAK inhibitor in combination with PD-1 antibody across preclinical models has led to 3 ongoing clinical trials combining our FAK inhibitor defactinib with anti-PD-1 and anti-PD-L1 in solid tumor indications. Additionally, in preclinical models, PI3K-delta inhibition has been shown to confer selective inhibition of Tregs, while PI3K-gamma inhibition confers selective inhibition of MDSCs. Accordingly, immuno-oncology applications of our Phase III PI3K-delta/gamma inhibitor duvelisib will be discussed.

11:45 New Tools for Exploring Immuno-Oncology Biology and Discovering Novel Signatures

Alessandra Cesano, Chief Medical Officer, NanoString Technologies

To facilitate the next wave of discoveries in IO biology and signature development, Nanostring has developed 2 new tools. First, the IO 360 Gene Expression Panel and Analysis Services focus on understanding the complex interplay of the tumor, microenvironment, and immune system to identify signatures of potential clinical relevance. Second, Nanostring has developed a platform enabling Digital Spatial Profiling of highly multiplexed RNA and protein targets in IO tumor tissue.

12:15 pm Session Break

12:25 Luncheon Presentation I: From Syngeneic to Humanized Mouse Models: Addressing the Needs for Novel Immunotherapies

Jean-Francois Mirjolet, Technology Director, Oncodesign

Discovery of novel immunotherapy represents a main and intense focus of reseach in oncology . Proof of concept studies in animal represent a challenge and require a well characterized and appropriate animal models with most of the time customized approaches. Some recent development and data generated for immune checkpoint modulators, adoptive cell tranfer therapy, vaccines and bispecific T cell engagers will be presented.

12:55 Luncheon Presentation II (Sponsorship Opportunity Available)  

1:25 Refreshment Break in the Exhibit Hall with Poster Viewing

ADVANCED TUMOR MODELING

2:00 Chairperson’s Remarks

Siwen Hu-Lieskovan, M.D., Ph.D., Assistant Clinical Professor, Department of Medicine, Division of Hematology-Oncology, David Geffen School of Medicine UCLA

2:10 Pre-Clinical Models of Small Cell Lung Cancer and the Validation of Therapeutic Targets

Julien Sage, Ph.D., Professor of Pediatrics, Hematology/Oncology, Genetics, Stanford University

Small cell lung cancer (SCLC) is the most lethal form of lung cancer. We will discuss the functional validation of novel therapeutic targets in SCLC based on human cancer genomic data and pre-clinical mouse models, including recent work on the Notch signaling pathway.

2:40 Enhancing T-cell-Mediated Tumor Killing

Shane R. Horman, Ph.D., Research Investigator III, Functional Genomics, GNF-Novartis

Deconvoluting and enhancing T-cell-mediated tumor killing is a central focus of immuno-oncology initiatives. We have developed a novel microphysiological 3D assay platform that quantitates T-cell-mediated killing of colorectal cancer tumor spheroids and enables parallel assessment of spheroid size and viability as well as T-cell penetration into the microtumor structure. Employing this assay platform in industrialized drug discovery, we profiled 1,800 annotated compounds and found a variety of targets that can be modulated to improve tumor-specific T-cell cytotoxicity.

3:10 Human Tissue Based Models in Immune-Oncology

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

3:40 The NANT Cancer Vaccine

David Pyrce, Ph.D., Senior Vice President, Innovation & Chief Commercial Officer, NantKwest, Inc.

The NANT Cancer Vaccine is an integrated, molecularly informed, multi-agent immunotherapy combining off-the-shelf natural killer cell therapy with adenoviral and yeast-based cancer vaccines designed to induce innate and adaptive immune responses in patients with cancer.

4:10 Valentine’s Day Celebration in the Exhibit Hall with Poster Viewing

5:00 Breakout Discussions in the Exhibit Hall

These interactive discussion groups are open to all attendees, speakers, sponsors, & exhibitors. Participants choose a specific breakout discussion group to join. Each group has a moderator to ensure focused discussions around key issues within the topic. This format allows participants to meet potential collaborators, share examples from their work, vet ideas with peers, and be part of a group problem-solving endeavor. The discussions provide an informal exchange of ideas and are not meant to be a corporate or specific product discussion.

6:00 Close of Day

Wednesday, February 14

7:00 am Breakfast Presentation (Sponsorship Opportunity Available)  

7:30 Registration Open and Morning Coffee

8:00 Plenary Keynote Session (click here for more details)

10:00 Refreshment Break and Poster Competition Winner Announced in the Exhibit Hall

NEW AND EMERGING TARGETS

10:50 Chairperson’s Remarks

Pamela Ohashi, Ph.D., Director, Tumor Immunotherapy Program; Co-Director, Campbell Family Institute for Breast Cancer Research; Senior Scientist, Princess Margaret Cancer Centre

11:00 Regulation of Anti-Tumor Immunity

Pamela Ohashi, Ph.D., Director, Tumor Immunotherapy Program; Co-Director, Campbell Family Institute for Breast Cancer Research; Senior Scientist, Princess Margaret Cancer Centre

My lab has been evaluating mechanisms that regulate the CD8+ T cell response because of its important role in immune surveillance and tumor immunotherapy. We have evaluated both mouse models and human tumor infiltrating lymphocytes cultures and uncovered unique insights into immune regulation. In addition, we have been evaluating the relevance of different Tc subsets in immunity and will present data on the role of these cells in anti-tumor responses.

11:30 TIGIT: A Key Inhibitor of the Cancer Immunity Cycle

Jane Grogan, Ph.D., Principal Scientist, Cancer Immunology Research, Genentech

Through accumulation of genetic mutations, many tumors express antigens that can potentially elicit specific tumor immunity. However, tumors can also suppress these responses by activating negative regulatory pathways and checkpoints such as PD-1/PD-L1 and CTLA-4. Blocking these checkpoints on T cells has provided dramatic clinical benefit, but only a subset of patients exhibit clear and durable responses, suggesting that other mechanisms must be limiting the immune response.

12:00 pm Antagonism of PVRIG, a Novel Checkpoint Receptor, Potentiates Anti-Tumor Responses

Spencer Liang, Ph.D., Director, Immuno-Oncology, Compugen, Inc.

Beyond recent advances in cancer immunotherapy with CTLA-4 and PD-1 blockade, additional checkpoint receptors may represent promising targets. PVRIG is a novel co-inhibitory receptor of the DNAM/TIGIT axis. Expression of PVRIG and its ligand, PVRL2, were induced in human cancers compared to normal tissues. PVRIG antagonism enhanced human T cell activation alone and combination with PD-1 or TIGIT inhibitors synergistically increased lymphocyte function. PVRIG-/- mouse T cells displayed enhanced function and tumors had delayed growth in PVRIG-/- as compared to WT mice. Anti-PVRIG antibody also significantly reduced tumor growth in combination with anti-PD-L1 or when administered to TIGIT-/- mice. In summary, PVRIG and PVRL2 were induced in cancer and that targeting PVRIG may be a novel treatment for cancer.

12:30 Session Break

12:40 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:10 Dessert Break in the Exhibit Hall and Last Chance for Poster Viewing

AGONIST - CHECKPOINT COMBINATION STUDIES

1:50 Chairperson’s Remarks

Deborah Law, D.Phil., CSO, Jounce Therapeutics

2:00 Activation of Myeloid IL-27 Production Initiates 4-1BB Agonist Hepatotoxicity

Michael A. Curran, Ph.D., Assistant Professor, Immunology, MD Anderson Cancer Center

The clinical progression of 4-1BB agonist antibodies has been stymied by limited understanding of their underlying mechanism of action and the resulting inability to separate off-target liver toxicity from on-target anti-tumor immunity. By analyzing the mechanisms underlying this toxicity, we have revealed novel insights into 4-1BB biology which can inform design of novel antibodies or combination strategies which favor tumor clearance over liver inflammation.

2:30 ATOR-1015, a Bispecific Immunomodulatory Antibody Targeting OX40 and CTLA-4

Christina Furebring, Ph.D., Senior Vice President, R&D, Alligator Bioscience

Alligator Bioscience has developed a bispecific antibody targeting OX40 and CTLA-4 for immunotherapy of cancer. The mode of action of ATOR-1015 includes depletion/suppression of regulatory T cells as well as activation of effector T cells. The design and the pharmacodynamics properties, as well as the biochemical properties and manufacturability, will be presented. ATOR-1015 is currently in preclinical development for clinical trials.

3:00 Preclinical and Phase I Safety and PK Evaluation of JTX-2011, a Novel ICOS Agonist Antibody

Deborah Law, D.Phil., CSO, Jounce Therapeutics

ICOS (Inducible T cell CO-Stimulator) is a co-stimulatory molecule expressed primarily on T lymphocytes. ICOS was prioritized as a target based on preclinical and clinical data suggesting it plays an important role in the immune response to cancer. JTX-2011 is an ICOS agonist antibody designed to shift the balance in tumors from immunosuppressive towards anti-tumor activity by stimulating T effector cells and reducing intratumoral T regulatory cells. Preclinical data assessing activity of JTX-2011, as well as in silico and IHC analysis and assessment of potential predictive biomarkers using an ex vivo tumor histoculture, helped inform the clinical study design. The preclinical data and safety evaluation of JTX-2011 from the Phase I portion of the biomarker-driven ICONIC trial will be described.

3:30 Session Break

NEXT-GENERATION CHECKPOINT INHIBITORS

3:40 Chairperson’s Remarks

Xingxing Zang, Ph.D., Associate Professor, Microbiology and Immunology & Medicine, Albert Einstein College of Medicine

3:45 TIGIT Checkpoint Blockade by mAb EOS884448 Restores T Cell Effector Functions and Display Anti-Tumor Efficacy

Gregory Driessens, Ph.D., Head, In Vivo Pharmacology, iTeos Therapeutics SA

4:15 Preclinical Evaluation of GITRL-Fc

Angie Inkyung Park, Ph.D., Senior Director, Immunotherapy and Stem Cells, OncoMed Pharmaceuticals

A novel single-gene linkerless GITRL trimer fused to an immunoglobulin Fc domain (GITRL-Fc) was generated and tested for its anti-tumor activity in preclinical tumor models. GITRL-Fc showed potent anti-tumor activity in several preclinical tumor models by inducing Th1-biased anti-tumor immunity and reducing Treg-mediated immune suppression. Combination of GITRL-Fc with PD-1 blockade significantly reduced the tumor growth in non-inflamed cold tumors. GITRL-Fc can improve cancer treatment by enhancing both innate and adaptive cellular immunity.

4:45 New Immune Checkpoints for Human Cancer Immunotherapy

Xingxing Zang, Ph.D., Associate Professor, Microbiology and Immunology & Medicine, Albert Einstein College of Medicine

CTLA-4 and the PD-1/PD-L1 pathway are current focuses for cancer immunotherapy. This presentation will discuss other new immune checkpoints for future human cancer immunotherapy.

5:15 Close of Conference Program

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