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
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 S. Chadwick, PhD, Director of Biologic Development, BioAnalytix, Inc.; Co-Chair, Mentors Advisors and Peers Program, Women In Bio, Boston Chapter
Panelists:
Joanna Brewer, PhD, Vice President, Platform Technologies, AdaptImmune
Charlotte A. Russell, MD, DMSc, CMO, Alligator Bioscience
Susan Richards, PhD, Presidential Scientific Fellow, Translational Medicine Early Development, Sanofi R&D
Kristi Sarno, Senior Director, Business Development, Pfenex
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 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
Stephen 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
John 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
Caroline
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
Patrik 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
Graeme 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
Inanc 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
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
Martine
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
Keri Streby, MD, Pediatric
Oncologist, Hematology & Oncology, Nationwide Children’s Hospital
3:15 Rational Engineering of Recombinant Vaccinia Viruses for Cancer Immunotherapy
Liang 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)
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
Brian 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
Timothy 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
Samuel 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)
11:05 Exploring Virotherapy/Immunotherapy Combinations for the Treatment of Glioblastoma
Sean 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
Smita 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
Per 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