Oncolytic Viral Therapy

 

Oncolytic virotherapy may be the next major breakthrough in immunotherapy. Long viewed as tools for directly killing cancer cells, recent research indicates that oncolytic viruses may have a bigger role to play by triggering an immune response in the body against cancer. Interest in the field is at an all-time high, evidenced by the entry of big pharma the likes of Amgen, Pfizer, Celgene, BMS, as well as many smaller but highly active biotech companies.

Acknowledging the importance and growing interest in this field, CHI is bringing the first annual Oncolytic Viral Therapy to PEGS Boston. The conference will present exciting research and development in the field, from mechanistic understanding of viruses and tumor biology to engineering and optimization strategies, preclinical and translational sciences, clinical trial updates and challenges.

Final Agenda

TUESDAY, APRIL 9

Recommended Short Course*

SC10: CAR T-Cell Therapy for Solid Tumors

Soldano Ferrone, MD, PhD, Division of Surgical Oncology, Surgery, Massachusetts General Hospital, Harvard Medical School

 

Moonsoo M. Jin, PhD, Professor, Biomedical Engineering, Radiology & Surgery, Molecular Imaging Innovations Institute, Weill Cornell Medical College

Tara Arvedson, PhD, Director, Oncology Research, Amgen 

 

*Separate registration required.

WEDNESDAY, APRIL 10

7:15 am Registration (Commonwealth Hall) and Morning Coffee (Harbor Level)

7:25 - 8:25 PANEL DISCUSSION: Women in Science – Inspired Professional and Personal Stories (Continental breakfast provided) (Waterfront 1&2)

Moderator:

Jennifer-ChadwickJennifer S. Chadwick, PhD, Director of Biologic Development, BioAnalytix, Inc.; Co-Chair, Mentors Advisors and Peers Program, Women In Bio, Boston Chapter


Panelists:

Joanna BrewerJoanna Brewer, PhD, Vice President, Platform Technologies, AdaptImmune


Charlotte A. RussellCharlotte A. Russell, MD, DMSc, CMO, Alligator Bioscience


Susan RichardsSusan Richards, PhD, Presidential Scientific Fellow, Translational Medicine Early Development, Sanofi R&D


Kristi SarnoKristi Sarno, Senior Director, Business Development, Pfenex


ENGINEERING NEXT-GEN ONCOLYTIC VIRUSES

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8:30 Chairperson’s Opening Remarks

Timothy Cripe, MD, PhD, Professor and Chief, Division of Hem/Onc/BMT, Nationwide Children’s Hospital


8:40 KEYNOTE PRESENTATION: Next Generation OV and New Combinational Approaches for Treatment of Solid Tumors

Paola GrandiPaola Grandi, PhD, CSO, Cold Genesys

In the last few years, oncolytic vectors have become one of the most promising immuno-therapy agents for the treatment of cancer. Leaders from academia and industry have made advances in vector engineering, explored advantages and limitations of preclinical models, discussed updates from combination trials, as well as shared challenges and potential strategies of systemic delivery. In this talk, I will present an overview of the Phase II clinical trial with CG0070 for the treatment of BCG-unresponsive bladder cancer.

9:10 Antibody Targeted Viruses: The Next Generation of Oncolytics

Russell_StephenStephen J. Russell, MD, PhD, CEO, Vyriad, Inc.

Oncolytic virus potency can be favorably impacted by concomitant immunosuppressive drug therapy to retard the host antiviral response and accelerate intratumoral spread. But without stringent targeting of virus tropism, increased OV potency is associated with an increased risk of off-target toxicity. To address this limitation, Vyriad is developing a new generation of retargeted viruses whose attachment, cell entry and cytotoxic potential are fully reprogrammed through surface display of single chain antibody targeting domains.

9:40 Oncolytic Virus Vaccines

Bell_JohnJohn C. Bell, PhD, Professor, Medicine & Biochemistry, Microbiology & Immunology, Ottawa Hospital Research Institute, University of Ottawa


10:10 Coffee Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)

10:15 Women in Science Speed Networking in the Exhibit Hall (Commonwealth Hall)

10:55 Engineering Viruses to Deliver their Maximum Potential: Two Examples from the Turnstone Portfolio

Breitbach_CarolineCaroline Breitbach, PhD, Vice President, R&D Programs and Strategy, Turnstone Biologics

An overview of the development of MG1 Maraba an SKV vaccinia oncolytic viral immunotherapy platforms will be provided. MG1 is a novel rhabdovirus engineered to express tumor antigens, thereby eliciting anti-tumor immune responses while modifying the tumor immune microenvironment. SKV is a novel engineered vaccinia platform being used to deliver multiple immune-modulatory agents. These therapeutic agents are designed to re-program the tumor microenvironment to abrogate immunosuppressive networks, thereby re-establishing endogenous anti-tumor immunity to achieve an effective in situ vaccination.

11:25 VSV-GP Eradicates the Tumor and Stimulates an Immune Response

Erlmann_PatrikPatrik Erlmann, PhD, Head, R&D, ViraTherapeutics GmbH

VSV-GP combines the tumor cell killing efficacy of Vesicular Stomatitis Virus with an enhanced safety profile, making it an excellent oncolytic virus candidate for clinical development. Here we show that VSV-GP mediated cell lysis releases tumor derived antigens, which in combination with the viral components, such as the viral RNA genome unleash a strong anti-tumor immune response.

11:55 PRESENTATION CANCELLED: Talimogene Laherparepvec - The Journey So Far and the Horizon Beyond

Hacking_GraemeGraeme Hacking, PhD, Medical Director, Amgen, Inc.

T-Vec is the first FDA-approved viral oncolytic. Preclinical and clinical trial data will be presented, as well as a status update on currently ongoing trials.

 12:25  NEW TIME: 11:55 POSTER HIGHLIGHT: Stealth Targeted Nano Coatings for Oncolytic Viruses for Repeat Systemic Administration

Ortac_InancInanc Ortac, PhD, CTO, DevaCell, Inc.

Systemic delivery and repeat administration of oncolytic viruses have been shown to be crucial for strong efficacy and anti-tumor immunity of oncolytic virotherapy. However, rapid neutralization and clearance of oncolytic viruses limits the promise of the therapy. Surface modifications of viruses such as blocking and removing immunogenic antigens often have negative impacts on the infectivity of the virus. This poster describes a novel approach, which is based on forming a removable organic/inorganic hybrid nanolayer, ONCoat™, formed around the virus surface that releases the unmodified virus inside the infected cell. Such encapsulation provides flexible surface functionalization to the virus while allowing viruses to be stealth to the immune system, enabling targeted syste mic delivery and repeat administration. Following application of ONCoat™, the infectivity of the virus is not negatively affected. Furthermore, virus, when released within the cell, is unmodified can still engage its own mechanisms for gene expression, replication and oncolysis.

12:55 NEW TIME: 12:25pm Enjoy Lunch on Your Own

1:55 Session Break

PRECLINICAL AND CLINICAL PROGRESS

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2:10 Chairperson’s Remarks

Patrik Erlmann, PhD, Head, R&D, ViraTherapeutics GmbH

2:15 Development of Patient-Derived Glioblastoma Model Systems to Predict Response to OV Therapy

Lamfers_MartineMartine Lamfers, PhD, Associate Professor, Neurosurgery, Erasmus Medical Center Rotterdam

Oncolytic viral therapies are showing promising results in early clinical trials, however, response rates are suboptimal. Preclinical studies suggest that tailoring the selected OV strain to the tumor subtype may markedly improve response rates. Patient-derived model systems may offer a tool to identify the most optimal oncolytic virus for a specific patient and could aid in the design of future stratified trials for OV therapy.

2:45 Lessons Learned from a Phase I Trial of Intratumoral and Intravenous Oncolytic Herpes Virus in Children and Young Adults

Streby_KeriKeri Streby, MD, Pediatric Oncologist, Hematology & Oncology, Nationwide Children’s Hospital


3:15 Rational Engineering of Recombinant Vaccinia Viruses for Cancer Immunotherapy

Deng_LiangLiang Deng, MD PhD, Associate Member, Associate Attending Physician, Memorial Sloan Kettering Cancer Center

Preclinical and clinical studies have shown that viral-based immunotherapy has the potential to overcome resistance to immune checkpoint blockade and to fill the unmet needs of many cancer patients. Vaccinia virus is a cytoplasmic DNA virus that was used successfully for the eradication of smallpox. Modified vaccinia virus Ankara (MVA) is a highly attenuated, effective, and safe vaccinia strain that is an important vaccine vector. We recently showed that intratumoral (IT) delivery of inactivated modified vaccinia virus Ankara (iMVA) induces antitumor systemic immunity via the STING-mediated cytosolic DNA-sensing pathway and Batf3-dependent CD103+/CD8a+ dendritic cells (DCs). Moreover, when compared with monotherapy alone, the combination of IT iMVA and systemic delivery of immune checkpoint blockade antibodies led to enhanced efficacy (Dai and Wang et al. Science Immunology, 2017). In this presentation, I will discuss our efforts in engineering recombinant MVA and vaccinia viruses, which removes viral immune-suppressive genes and expresses immune-activating transgenes to improve antitumor effects in preclinical tumor models.

3:45 Refreshment Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)

4:45 Problem-Solving Breakout Discussions - Click here for details (Commonwealth Hall)

5:45 Networking Reception in the Exhibit Hall with Poster Viewing (Commonwealth Hall)

7:00 End of Day

THURSDAY, APRIL 11

8:00 am Registration (Commonwealth Hall) and Morning Coffee (Harbor Level)

TARGETING THE TUMOR MICROENVIRONMENT

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8:30 Chairperson’s Remarks

Paola Grandi, PhD, CSO, Cold Genesys

8:35 T-SIGn Virus Approach to Cancer Gene Therapy – Driving the Tumor Cells to Express Combinations of Biological Therapeutics within the Tumor Microenvironment

Champion_BrianBrian Champion, PhD, CSO, PsiOxus

This presentation will cover the T-SIGn oncolytic adenovirus platform: gene therapy for cancer; T-SIGn viruses for combination immunotherapy and NG-641 T-SIGn virus designed for targeting the treatment of stromal-rich cancers.

9:05 Inflaming the Tumor Microenvironment to Augment Oncolytic Virotherapy

Cripe_TimothyTimothy Cripe, MD, PhD, Professor and Chief, Division of Hem/Onc/BMT, Nationwide Children’s Hospital

Cancer immunotherapies hold great promise, but scores of disappointing studies highlight our relative ignorance in understanding the immunosuppressive microenvironment within solid tumors. Because of their central role in mediating immunosuppression, tumor associated macrophages (TAMs), typically “polarized” to a so-called M2-like phenotype, are thought to be an important therapeutic target. I will discuss our work to modulate TAMs and TGFb to enhance antitumor efficacy of oncolytic herpes virotherapy.

9:35 Oncolytic Herpes Simplex Virus Combinations Boosting Immunovirotherapy

Rabkin_SamuelSamuel D. Rabkin, PhD, Thomas A. Pappas Prof in Neurosciences, Prof of Neurosurgery (Microbiology), Harvard Medical School and Massachusetts General Hospital

Oncolytic herpes simplex virus (oHSV) acts by direct tumor cell killing and the induction of anti-tumor immune responses, immunovirotherapy.  The virus can also be 'armed' with therapeutic transgenes, such as cytokines, to improve efficacy by modulating the tumor microenvironment.  We will describe preclinical studies to boost immunovirotherapy using oHSV combinations with approved pharmacological agents targeting oncogenic pathways (MEK inhibitors) and the tumor microenvironment (axitinib). These combinations can interact with immune checkpoint blockade and are translatable to the clinic.

10:05 Coffee Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)

COMBINATION VIROTHERAPY WITH IMMUNOTHERAPY

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11:05 Exploring Virotherapy/Immunotherapy Combinations for the Treatment of Glioblastoma

Lawler_SeanSean Lawler, PhD, Assistant Professor, Managing Director, Harvey Cushing Neurosurgery Laboratories, Brigham and Women’s Hospital

We have been investigating a gene therapy agent based on a non-replicating adenoviral vector to deliver the Herpes virus Thymidine kinase gene to glioblastoma by intratumoral injection. Our studies have shown that this results in high local IFNg levels, and upregulation of PD-L1 on tumor cells, microglia, and macrophages in the tumor microenvironment. Combination of immune checkpoint blockade with an anti-PD1 antibody overcomes this potential resistance mechanism and leads to a high cure rate in experimental murine glioblastoma models. This combination is now being advanced towards Phase I clinical trials in primary glioblastoma.

11:35 Oncolytic Poliovirus Combined with PD1/PDL1 Blockade for Cancer Therapy

Nair_SmitaSmita Nair, PhD, Professor, Surgery, Neurosurgery and Pathology, Duke University School of Medicine

Oncolytic poliovirus PVSRIPO targets and kills tumor cells and induces sustained type I IFN-dominant activation of antigen presenting cells, which overcomes the immunosuppressive tumor microenvironment to stimulate antitumor immunity. Preclinical data in murine models demonstrate that: 1] Intratumor PVSRIPO administration causes oncolysis and inflammation, which stimulates innate and adaptive immunity; 2] Immune activation triggers adaptive immune resistance via the PD1/PDL1 axis; 3] Blocking PD1/PDL1 with PVSRIPO eliminates adaptive resistance and potentiates durable antitumor immunity.

12:05 pm Combination of Adenovirus Oncolytic Virotherapy with CDK4/6 Inhibitors: An Unexpected and Incredible Strong Treatment Alliance

Holm_PerSonnePer Sonne Holm, PhD, Head, Virotherapy Research Group, Urology, Technical University Munich

It is widely accepted that adenovirus E1A drives human cells into S-phase by displacing the Retinoblastoma (RB) proteins from E2F transcription factors to de-repress cell cycle genes and viral gene expression. However, CDK4/6 inhibitors led to strong synergistic effects with regards to viral replication and cell killing, resulting in new unexpected insights into Rb/E2F regulation of adenovirus life cycle. These new perspectives in the Rb/E2F mediated regulation of the adenoviral life cycle will have great impact for the use of oncolytic adenoviruses with cell cycle inhibitors.

12:35 End of Oncolytic Viral Therapy


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