While cancer immunotherapy has made a giant leap in the past five years, the majority of therapies at advanced stages of development are clustered in a similar target space. The increased investment in immuno-oncology has created an urgent opportunity to discover and populate new target spaces that either present new classes of immunotherapies or can be used in combination with existing products. Cambridge Healthtech Institute’s Inaugural Emerging Immuno-Oncology Targets conference will cover the emerging target space, including immunomodulatory inhibitor and agonist targets, stromal and immune cell targets, and strategies for rational combination immunotherapy. Case studies of preclinical and translational approaches to the discovery and validation of new immuno-oncology targets and combinations will be presented.
THURSDAY, AUGUST 31
7:45 am Registration & Morning Coffee
8:25 Chairperson’s Opening Remarks
Angie Inkyung Park, Ph.D., Senior Director, Immunotherapy and Stem Cells, OncoMed Pharmaceuticals
8:30 TIM-3 Biology in Myeloid Cells and Implications for TIM-3 Blockade in Immuno-Oncology
Xiaomo Jiang, Ph.D., Investigator, Immuno-Oncology, Novartis Institutes for BioMedical Research
TIM-3 has critical roles in tumor-induced immune suppression on a multitude of cell types. TIM-3 blockade to activate immune response and control tumor growth could reflect the combined effects on modulating not only the functional phenotype of dysfunctional effector T cells, but also inhibiting the suppressive activity of various suppressor cells.
9:00 Exploring Checkpoint Biology in Syngeneic Mouse Models
Fiona Sharp, Ph.D., Investigator II, Exploratory Immuno-Oncology, Novartis Institutes for BioMedical Research
The role of checkpoint proteins in regulating anti-tumor immunity has by now been well established for multiple proteins, including PD-1/PD-L1, LAG-3 and TIM-3. While the cellular and ligand interaction targets for some of these proteins are well defined, our knowledge of these aspects of TIM-3 requires further investigation. Gaining better insight into the key players in TIM-3 biology is central to enhancing the efficacy of this target in the clinic. Our studies have been focused on further exploring the key immune cells involved in TIM-3 controlled anti-tumor immune responses in syngeneic mouse models.
9:30 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.
10:00 Coffee Break in the Exhibit Hall (Last Chance for Poster Viewing)
10:45 Preclinical and Clinical Activity of the CD27 Agonist Antibody Varlilumab
Tibor Keler, Ph.D., Senior Vice President & CSO, Celldex Therapeutics
In preclinical models, varlilumab’s agonist properties that lead to immune activation need to be coupled with its deleterious effect on Tregs to achieve potent antitumor activity across multiple models. A similar profile of immune activation and reduction in Tregs has been observed in cancer patients treated with varlilumab. Significant efforts are underway to correlate these biomarkers with clinical endpoints to inform dose and patient selection.
11:15 Preclinical Evaluation of GITR Ligand
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/PDL1 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.
11:45 Targeting IDO1 to Enhance Cancer Immunotherapy: Not So Simple After All
Derek A. Wainwright, Ph.D., Assistant Professor, Departments of Neurological Surgery, Microbiology-Immunology, and Division of Hematology-Oncology, Northwestern University Feinberg School of Medicine
IDO1 is canonically-recognized as an inducible enzyme that converts tryptophan into kynurenine. In cancer immunology, IDO1 has been associated with contributing to immunosuppression of the anti-tumor immune response. However, tryptophan depletion and/or kynurenine accumulation does not fully account for IDO1-mediated immune evasion by cancer cells. Utilizing syngeneic and humanized mouse models of glioblastoma (GBM), in addition to the analysis of patient-resected tumors, new aspects of IDO1 will be described.
12:15 pm Sponsored Presentation (Opportunity Available)
12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:15 Session Break
2:25 Chairperson’s Remarks
Jennifer Wu, Ph.D., Professor, Feinberg School of Medicine; Director, Cancer Immunology Program, Robert Lurie Comprehensive Cancer Center, Northwestern University
2:30 KEYNOTE PRESENTATION: Elements of Rational Combination Development in Cancer Immunotherapy
Edward Cha, M.D., Ph.D., Associate Medical Director, Cancer Immunotherapy Franchise, Genentech
The tumor microenvironment plays an important role in inhibiting the propagation of effective cancer immunity. Although PD-L1 is a critical source of immune suppression, additional elements in this environment also determine whether cancers successfully are eradicated or evade the immune response. This talk will focus on approaches to targeting immune escape mechanisms through novel agents and combinations, and on clinical designs that support more efficient discovery.
3:00 Pharmacodynamics and Antitumor Activity of the Adenosine 2A Receptor Antagonist AZD4635
Rich Woessner, Ph.D., Principal Scientist, IMED Oncology, AstraZeneca Pharmaceuticals
AZD4635 is a potent and highly selective antagonist of adenosine-mediated A2A receptor signaling, and inhibits T-cell function in ex vivo assays. In murine tumor models, oral administration of AZD4635 increases the expression of genes associated with immune activation, increases expression of co-stimulatory markers on antigen presenting cells, and enhances the antitumor activity of anti-PD-L1 antibody treatment. AZD4635 is in clinical evaluation as a single agent and in combination with the anti-PD-L1 antibody durvalumab.
3:30 Refreshment Break
4:00 Beyond Immune Checkpoint: Targeting Soluble NKG2D Ligands for Cancer Immunotherapy
Jennifer Wu, Ph.D., Professor, Feinberg School of Medicine; Director, Caner Immunology Program, Robert Lurie Comprehensive Cancer Center, Northwestern University
Human tumor-derived soluble NKG2D ligand sMIC is highly immune suppressive and thus an emerging target for cancer immunotherapy. Using a clinically relevant mouse model, we show that therapy with the non-blocking sMIC-neutralizing antibody resulted in effective debulking primary tumors and eliminating metastases. Neutralizing sMIC also synergistically enhanced tumor response to PD-1 and CTLA4 immune checkpoint blockade therapy. These findings launched a new avenue of combination cancer immunotherapy.
4:30 KEYNOTE PRESENTATION: Bispecifics to the Rescue: Reviving Exhausted T Cells with Dual Costimulation
Raphael Clynes, M.D., Ph.D., Vice President, Translational Biology, Xencor
5:00 Development of TGFβ Inhibitors for Immune-Oncology
Rikke Holmgaard, Ph.D., Senior Research Scientist, Eli Lilly
The transforming growth factor β (TGFβ) signaling pathway is a pleiotropic cellular pathway that plays a critical role in cancer. In fact, aggressive tumors are typically associated with high ligand levels and thus associated with poor prognosis in various tumor types. Here we describe the identification of inhibitors targeting the TGFβ pathway and provide proof of concept data supporting the role of TGFβ in cancer and the utility of targeting the TGFβ pathway.
5:30 End of Day
6:00 Dinner Short Course Registration*
Recommended Dinner Short Courses*
SC4: CRISPR/Cas9 Applications in Immunotherapy
*Separate registration required, please click here for more information.
FRIDAY, SEPTEMBER 1
8:00 am Registration and Morning Coffee
8:25 Chairperson’s Opening Remarks
Shane Olwill, Ph.D., Vice President, Head of Development & Immuno-Oncology, Pieris Pharmaceuticals GmbH
8:30 Costimulatory T-Cell Engagement by the 4-1BB/HER2 Bispecific PRS-343 for Tumor Localized Activation of the Immune System
Shane Olwill, Ph.D., Vice President, Head of Development & Immuno-Oncology, Pieris Pharmaceuticals GmbH
PRS-343 is a bispecific monoclonal antibody/Anticalin fusion protein comprised of a HER2 tumor-targeting mAb genetically linked to a potent Anticalin specific for the immune costimulatory TNF family receptor 4-1BB (CD137). PRS-343 is being developed as the first 4-1BB based therapeutic to mediate the activation of tumor-specific T lymphocytes selectively within the tumor microenvironment (TME). 4-1BB is a potent costimulatory immunoreceptor and an established marker for tumor-specific infiltrating T lymphocytes (TILs), and is therefore, an attractive target for cancer immunotherapy. In in vivo preclinical tumor models, PRS-343 has demonstrated potent T lymphocyte activation localized to the TME of established HER2-positive tumors, indicating the potential for both enhanced safety and efficacy.
9:00 Dual Targeting Bispecific Antibodies Selectively Block Innate Immune Checkpoint Receptor CD47 on Tumor Cells
Stefano Majocchi, Ph.D., Research Scientist, Novimmune SA
CD47, a ubiquitously expressed innate immune checkpoint receptor that serves as a universal “don’t eat me” signal of phagocytosis, is often up-regulated by hematological and solid cancers to evade immune surveillance. We generated dual-targeting bispecific antibodies capable of selective inhibition of CD47 on malignant cells through co-engagement of a tumor-associated antigen (TAA). This dual-targeting approach exploits an innovative cancer immunotherapy mechanism while avoiding a poor pharmacological half-life and potential hematological toxicities which are observed when CD47 is indiscriminately blocked. Such bispecific antibodies lead to TAA-dependent cancer cell killing through ADCP and ADCC in vitro and show anti-tumor activity in vivo associated with long pharmacokinetic half-life and absence of toxicity.
9:30 Predicting the Efficacy and Safety Profile of ImmTAC™ Molecules: The Preclinical Challenge
Martina Canestraro, Ph.D., Senior Scientist, Preclinical Biology, Immunocore, Ltd.
ImmTAC™ molecules consist of an affinity enhanced T cell receptor fused to an anti-CD3 specific scFv. Since both ends of the molecule are human specific, standard species tox models are not appropriate for ImmTAC safety testing. This presentation will provide an overview of our technology and of the in vitro preclinical approach that was used to predict the safety and efficacy profile of our most advanced molecule IMCgp100, currently in Phase II clinical trials for the treatment of cutaneous and uveal melanoma.
10:00 Coffee Break
10:30 Discovery and Development of Novel Immunogenic Tumor Neoantigens for the Treatment of Solid Tumors
Philip M. Arlen, M.D., President & CEO, Precision Biologics, Inc.
Immunogenic neoantigens were derived from a membrane preparation of pooled allogeneic colorectal cancer from patients undergoing surgery. Membrane fractions were isolated and tested for immunogenicity and utilized in a clinical trial in patients with chemotherapy refractory metastatic colorectal cancer. A positive correlation was observed in patients who were able to mount and sustain IgG responses to vaccine. Antibodies were screened using this vaccine and tested for sensitivity, specificity, and anti-tumor function. Neoantigens were identified in colon cancer with these functional antibodies.
11:00 Neoantigen Identification by Human Tumor Immunopeptidomics, NGS, and Deep Learning
Roman Yelensky, Ph.D., CTO, Gritstone Oncology
Genetic instability is a hallmark of cancer and, consequently, each cancer patient's tumor genome is different from their normal cells. This DNA difference leads to the creation of new protein antigens that are specific to tumor cells. These new antigens, known as tumor-specific neoantigens, can be recognized and targeted by the immune system. Gritstone Oncology is exploiting this vulnerability of tumor cells by identifying a patient's unique set of tumor antigens and deploying them in a therapeutic immunization strategy. Current approaches to neoantigen prediction from genomic sequence are limited in specificity and sensitivity. To build a best-in-class neoantigen prediction model, Gritstone collected large numbers of human tumors (initial focus on NSCLC) and characterized them by next-generation sequencing and HLA immunopeptidomics to measure HLA presented peptides. These data were used to build a neural network-based neoantigen prediction model that performs with high positive predictive value and offers broad HLA allelic coverage. Predicted neoantigens were further validated with in vitro T cell priming in HLA-matched systems.
11:30 High-Throughput Functional Screening of Neoantigens for Vaccines and TCR-Based Adoptive T Cell Therapies
Dolores J. Schendel, Ph.D., CEO & CSO, Medigene AG
Neoantigens are an important class of highly specific target molecules for various immunotherapies. In transiting from identification of mutant peptides by NGS and prediction of binding to HLA allotypes, Medigene explores high throughput technologies to functionally verify that predicted neoantigens do in fact lead to T cell recognition. Our rapid methods bypass the need for patient cells, overcoming logistical restrictions for determining the true immunogenicity of predicted neoantigens.
12:00 pm Close of Emerging Immuno-Oncology Targets