IMT


Target discovery remains critical in order to continue advancing immunotherapies. Much work has been done with antagonists PD-1/PD-L1 and CTLA-4, but there is an entire class of agonists still being explored. The Second Annual Agonist Immunotherapy Targets event will examine these modalities and their potential role in successful disease treatment. Agonists showing the most promise, including OX40, CD27, GITR, and 4-1BB, will be covered in clinical case studies by examining the data as well as the biology and mechanisms.  Emerging agonists, including TNFR receptors, ICOS, and VISTA will also be discussed. Focus will be given throughout to potential combination immunotherapies to ensure durable antitumor response. Overall, this event will emphasize strategies for target discovery to ensure continued growth and success for immunotherapies. 

THURSDAY, APRIL 28


CASE STUDIES WITH AGONIST BIOLOGICS

12:35 pm Luncheon in the Exhibit Hall with Poster Viewing

1:40 Chairperson’s Remarks

Deborah Charych, Ph.D., Executive Director, Research Biology, Nektar Therapeutics

1:50 Hexavalent TNF-Superfamily Mimics for Cancer Treatment and Immune Modulation

Oliver_HillOliver Hill, Ph.D., Vice President, Molecular Biology, Apogenix, GmbH

Apogenix has developed a fusion protein technology to create hexavalent agonists targeting individual members of the TNFR-superfamily. Compared to conventional approaches using agonistic antibodies, Apogenix’ compounds mimic the three-dimensional organization of the natural ligands (the TNFSF proteins). Consequently, their activity does not rely on secondary crosslinking events in vitro nor in vivo. We will present the molecular engineering concept and the current results obtained for the TRAIL-R-, CD40- and CD27-agonists.

2:20 NKTR-214: Harnessing the IL-2 Receptor Pathway for Cancer Immunotherapy

Deborah_CharychDeborah Charych, Ph.D., Executive Director, Research Biology, Nektar Therapeutics

The IL-2 pathway is a potent means of expanding tumor-killing CD8 T cells. However IL-2 also stimulates regulatory T cells (Tregs). NKTR-214 is an engineered cytokine designed for sustained and biased signaling of IL-2 receptors, significantly increasing CD8 T cells over Tregs in tumor. We will discuss the design of NKTR-214 and its significant anti-tumor activity in multiple mouse models. The agent is currently in Phase 1 for the treatment of solid tumors.

2:50 OX40: From Bench to Bedside

Brendan_CurtiBrendan D. Curti, M.D., Director, Genitourinary Oncology Research & Biotherapy Clinical Programs; Co-Director, Melanoma Program, Earle A. Chiles Research Institute, Providence Cancer Center

OX40 is a co-stimulatory pathway present in CD4 and CD8 T cells. Engagement of OX40 on antigen-exposed T cells results in enhanced memory and effector function. Numerous pre-clinical murine models show anti-tumor activity of OX40 agonists. The clinical development and immunologic changes induced by OX40 agonists in patients with cancer will be discussed along with pre-clinical work supporting the use of OX40 agonists with T cell checkpoint inhibitors and other immune modulators.

Pieris Pharmaceuticals3:20 Costimulatory T-Cell Engagement by the CD137/HER2 Bispecific, PRS-343, Leads to Tumor-Targeted Immune Modulation

Shane Olwill, Vice President & Head, Development, Pieris Pharmaceuticals Inc.

We report potent costimulatory T-cell engagement of the immunoreceptor CD137 in a tumor targeted manner, utilizing the CD137/HER2 bispecific, PRS-343. Compared to known CD137-targeting antibodies in clinical development, this approach has the potential to provide a more localized activation of the immune system with better therapeutic index. The positive functional ex vivo and in vivo data of PRS-343 as well as the excellent developability profile support investigation of its anti-cancer activity in clinical trials.

3:50 Refreshment Break

4:20 Experimental Approaches for Cancer Immunotherapy Using Anti-CD40 Antibody

Alexander_RakhmilevichAlexander Rakhmilevich, M.D., Ph.D., Distinguished Senior Scientist, University of Wisconsin-Madison

CD40 ligation has been shown to induce antitumor effects in mice and cancer patients. We have demonstrated in several syngeneic mouse tumor models that anti-CD40 antibody, alone and in synergy with a toll-like receptor 9 agonist, CpG, activates macrophages and induces T cell-independent antitumor effects. The antitumor efficacy of anti-CD40 and CpG can be further enhanced by chemotherapy or T cell activation approaches involving checkpoint blockade.

4:40 Generation of an Optimal Anti-Tumor Immune Response as Prime for Checkpoint Inhibition

Thomas_DavisThomas Davis, M.D., CMO & Executive Vice President, Clinical Development, Celldex Therapeutics

Combinations of immune modulators have shown marked synergy in preclinical studies and a range of combination studies are in progress. The combination of antigen specific vaccines with immune actuators, such as flt3L and agonist anti-CD27 antibodies, may offer improved responses to checkpoint as well as independent activity.

5:00 End of Day

5:15 Registration for Dinner Short Courses*


Recommended Dinner Short Course*

SC11: Clinical Prospects of Cancer Immunotherapy

*Separate registration required.


FRIDAY, APRIL 29

8:00 am Registration and Morning Coffee

EMERGING AGONIST AND ANTAGONIST TARGETS

8:30 Chairperson’s Remarks

Adam J. Adler, Ph.D., Professor, Immunology, School of Medicine, UConn Health

8:35 Unlocking the Full Potential of Agonist Antibodies: A Multi-Faceted Challenge

Nicholas Wilson, Ph.D., Senior Director, T Cell Biology, Agenus Inc.

Recent work on activating checkpoint targets such as GITR and OX40 has revealed that in addition to their co-stimulatory potential to enhance T cell responsiveness to tumor associated antigens, they are also highly expressed by activated intratumoral regulatory T cells. A more complete picture of the anti-tumor potential of GITR or OX40 agonist antibodies emerges when their regulatory T cell depleting capacity is considered. A review of selected findings supporting this picture will be presented.

9:05 Preclinical Evaluation of JTX-2011, an Anti-ICOS Agonist Antibody

Deborah_LawDeborah Law, D. Phil. CSO Jounce Therapeutics, Inc.

ICOS (inducible co-stimulator molecule), a member of the CD28 superfamily, is a co-stimulatory molecule expressed on T lymphocytes. We have generated agonistic anti-ICOS antibodies which are efficacious as monotherapies and in combination with anti-PD1 in multiple syngeneic tumor models. Mechanistic studies demonstrate enhanced cytotoxic CD8:T-regulatory cell ratios and preferential reduction in T-regulatory cells in the tumor microenvironment. JTX-2011, a species cross-reactive humanized antibody, has been selected for development. Evaluation of JTX-2011 in nonhuman primate models, including safety and PK parameters, will be presented. Our preclinical data provides rational for clinical development of JTX-2011 in solid tumor indications.

9:35 Immunoregulation by VISTA in the Tumor Microenvironment

J_Louise_LinesJ. Louise Lines, Research Scientist, Microbiology & Immunology, Dartmouth College

VISTA is a recently identified PDL1/PD1-like ligand/receptor that is being developed as a target for cancer immunotherapy. VISTA blockade is therapeutic in CT26 cancer and synergizes with PD1 blockade. VISTA is highly expressed on tumor infiltrating myeloid cells, and impacts on myeloid function. Tumors from anti-VISTA treated mice show increased myeloid cells overall, but decreased granulocytic-MDSCs. This unique feature of anti-VISTA treatment may explain why it works well in combination with anti-PD1.

10:05 Coffee Break


AGONISTS IN COMBINATION WITH OTHER MODALITIES

10:35 Exploiting Unexpected Properties of Combination OX40 Plus 4-1BB Agonist Costimulated T Cells for Tumor Immunotherapy

Adam_AdlerAdam J. Adler, Ph.D., Professor, Immunology, School of Medicine, UConn Health

Combining agonists to the costimulatory receptors CD134 and CD137 (dual costimulation) elicits potent T cell-mediated tumor immunity. Two approaches have been explored to further enhance therapeutic potency. First, engaging tumor-unrelated CD4 T cells that provide help to CD8 T cells in both antigen-linked and non-linked manners. Second, treatment with particular cytokine combinations (IL-12 or IL-2 plus IL-33 or IL-36) that trigger dual costimulated effector T cells via a TCR-independent mechanism.

11:05 Combinatorial Immunotherapy in Mouse Syngeneic Tumor Models

Hua Long, Senior Principal Scientist, Pfizer

Immunotherapies targeting the programmed death 1 (PD-1) coinhibitory receptor have shown great promise in the clinic. However, robust and safe combination therapies are still needed. We have investigated the antitumor activity of the anti-4-1BB/anti-PD-1 combination in the poorly immunogenic B16F10 melanoma model which resulted in pronounced tumor inhibition. The activity of the anti-4-1BB/anti-PD-1 combination was dependent on IFNγ and CD8(+) T cells and elicited a robust antitumor effector/memory T cell response. Combinatorial treatment with other agents will also be discussed.

11:35 Co-Stimulatory Agonists for the Immunotherapy of Cancer

Alan_EpsteinAlan L. Epstein, M.D., Ph.D., Professor, Pathology, USC Keck School of Medicine

Co-stimulation is a key step in the development of an effective immune response to tumors. RT-PCR and IHC show that the tumor microenvironment lacks these key agonists to hinder the immune destruction of tumors. Our data demonstrate that providing missing co-stimulation using intravenously administered Fc-fusion proteins can be synergistic with methods to reduce immune suppression to provide effective and lasting treatment of cancer as a new direction of cancer immunotherapy.

12:05 pm Enjoy Lunch on Your Own

1:05 Refreshment Break


STRATEGIES FOR TARGET DISCOVERY

1:35 Chairperson’s Remarks

Yoram Reiter, Ph.D., Professor & Head, Laboratory of Molecular Immunology, Technion-Israel Institute of Technology

Comprehensive Discovery of New Immuno-Oncology Targets

Art Brace, Ph.D., Executive Director, Immuno-Oncology Research, Five Prime Therapeutics

Antibodies targeting checkpoint pathways are transforming the treatment of cancer. We believe there are targets that remain to be discovered that address unmet needs. FivePrime has developed comprehensive protein libraries and multiple in vitro and in vivo discovery platforms that can interrogate virtually all cell surface proteins and secreted factors as IO targets. This systematic approach enables the selection of the best antibody targets and combinations for defined cancer populations.

2:10 Discovering New Immunotherapy Targets by Dissecting Subsets of Human Tumor Infiltrating Lymphocytes

Andrew_WeinbergAndrew D. Weinberg, Ph.D., Chief, Laboratory of Basic Immunology, Providence Cancer Center; Agonox, Inc.

Our group has been interrogating CD8 and CD4 T cell phenotypes within several different human tumor types. We have found common phenotypic themes that are selectively expressed within the tumor and not in the blood. Gene arrays have been performed within these subsets of TIL and we will discuss new immunotherapy approaches based on targeting these T cell specific subsets within the tumor.

2:40 Discovery and Validation of Novel Targets for Cancer Immunotherapy: Exploring the Untapped Intracellular Proteome for Antibody-Based Novel Therapeutics

Yoram_ReiterYoram Reiter, Ph.D., Professor & Head, Laboratory of Molecular Immunology, Technion-Israel Institute of Technology

The ability to generate T cell receptor like (TCRL) antibodies which bind HLA-peptide complexes on the surface of cells and are derived from intracellular-derived targets opens new possibilities for developing new therapeutic modalities. These antibodies can bind specifically to, and kill, the diseased cells. Thus, it transforms disease-specific targets that are expressed inside malignant cells into targets that can be recognized on the cell surface by soluble TCRL antibodies. This approach expands the pool of novel therapeutic antibodies beyond the limits of currently available antibodies.

3:10 End of Agonist Immunotherapy Targets


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


View By: