Summit4CI Speaker Series

Summit4CI Speaker Series

Previous Sessions

Session Eight: Back to top

Increasing Gene Therapy Vector Production Using Viral Sensitizer Molecules
Date: Thursday, May 6, 2021 | 1:45 - 3:00pm ET

Inefficient manufacturing processes can have several important implications during product development. The first and most obvious is cost of goods (COGs), which is driven upwards when GMP compliant material is required. Related are the practical considerations of manufacturing virus using an inefficient process, which means longer times to produce target amounts of virus, more substantial needs in personnel, physical space, and investments in infrastructure. Lastly, there is the issue of maximum feasible dose, where the maximum dose of a manufactured virus given to a patient is limited by the amount of virus that can be produced.

Viral Sensitizers (VSETMs) encompass a proprietary collection of small molecules that enhance the growth of viruses by transiently and efficiently overcoming cellular antiviral defenses. VSEs can be used in a range of applications such as improving virus manufacturing yield, improving tumor infection by oncolytic viruses, or transduction of cells by common gene therapy vectors like AAV, adenovirus, and lentivirus. Owing to different molecular mechanisms through which they operate, VSEs can be combined, adapted, and formulated for specific uses.

To improve lentivirus production, we employed high throughput screening and DOE methodology to develop a VSE formulation that could improve 3rd generation lentivirus production in adherent HEK293T cells (VSE-LentiTM). We designed a high-throughput method to identify single then multi-VSE compound formulations that enhance lentivirus production. Different transfection reagents, and production scales as well as commonly used lentivirus production enhancers were tested. We found VSE-LentiTM to be compatible with several transfection reagents (PEI Pro, lipofectamine, TransIT lenti). VSE-LentiTM was able to enhance lentivirus production whether added at the time of transfection or up to 24h prior to transfection. Enhancements in lentivirus production were observed over 72 hours, without a requirement to resupply compounds. Improvements in yield observed using VSE-LentiTM were condition-dependent but in pre-optimized conditions lentivirus production conditions, VSE-LentiTM led to >5X increase in TU/ml

Speakers

Jean-Simon Diallo
Elena Godbout

You can read more about this research project here:

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Session Seven: Back to top

Novel combination approaches for solid tumours: leveraging checkpoint inhibition and radiation therapy in renal cell carcinoma
Date: Wednesday, April 14, 2021 | 2:30 - 4:00 pm ET

Immune checkpoint blockers, such as Ipilimumab and Nivolumab, have been shown to improve the lifespan of patients with metastatic kidney cancer by unleashing our immune system. However, not every patient benefits from immunotherapy. Understanding the factors that indicate which patients are likely to benefit from treatment, or ways to help immunotherapy work better for more patients, are important, unmet needs. Removal of the primary kidney mass - in disease that has already spread - was shown over 20 years ago to be modestly beneficial for metastatic kidney cancer patients; however, recent studies cast doubt on this benefit in the current immunotherapy era.

Alternatively, highly focused radiation is a convenient, safe method to kill cancer cells that may also enhance our immune response. We hypothesize that combining immunotherapy and highly focused radiation will improve the treatment of kidney cancer for patients who initially present with widely spread disease. To address this hypothesis, we are conducting a randomized phase II clinical trial (CYTOSHRINK) to study the benefits of combining Ipilimumab/Nivolumab and radiation for metastatic kidney cancer patients. Further, our proposed studies interrogating host samples of tumor tissue, blood and stool from immunological and genomic perspectives will provide a deeper understanding of tumor biology at the start and changes during treatment with this novel combination strategy.

Speakers

Aly-Khan Lalani
Anand Swaminath
Jessica Irvine
Michael Surette
Deborah Maskens
Donna McCarty

You can read more about this research project here:

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Session Six: Back to top

Fighting Viruses with Viruses: Repurposing cancer vaccine platforms to fight the spread of COVID-19
Date: Wednesday, March 10, 2021 | 2 - 3 pm EST

Leveraging technologies and platforms initially developed for cancer therapies, this virtual seminar will provide an overview of the development and translation of a novel COVID-19 vaccine at the Ottawa Hospital Research Institute (OHRI).

By harnessing the immune stimulating power of oncolytic viruses, Drs. John Bell and Carolina Ilkow have developed a strategy to rapidly engineer and test COVID-19 vaccine candidates. Using this live virus vaccine approach, Dr. Bell and his team have seen very promising immune responses against COVID-19 in mouse models with their lead vaccine candidate and are currently testing their approach in large animal studies, with the goal of evaluating this vaccine in human clinical trials.

However, before this innovation can make it to the clinic, it needs to be manufactured to a scale and level of purity that would ensure that it is safe to be tested in people. The Biotherapeutics Manufacturing Centre- Virus Manufacturing Facility (VMF) has been manufacturing therapeutic viruses for use in clinical trials both domestically and abroad for the past 15 years. Located within the OHRI, the VMF has experience and expertise in both developing virus-specific manufacturing processes and in GMP production. Given its proficiency manufacturing therapeutic viruses, the VMF has pivoted quickly to adapt its processes to support the manufacture of virus-based COVID-19 vaccines, including Dr. Bell’s.

Researchers at the OHRI are taking advantage of their unique environment that provides access to the full complement of discovery, translation and clinical testing activities to accelerate new and innovative therapies for the benefit of Canadians. Within this framework, Dr. Bell will provide insight into the development of his team’s novel COVID-19 vaccine discovery, while its subsequent translation into a product suitable for clinical trials will be provided by the VMF’s Director, Dr. Jennifer Quizi, with an emphasis on the importance of training and HQP in biomanufacturing.

Speakers

Jennifer Quizi
John Bell
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Session Five: Back to top

"Engineered Biovesicles" - A new platform for cancer immunotherapeutics
Date: Monday, February 22, 2021 | 1:30 - 3:15pm EST

Biovesicles are a class of tiny synthetic or biological particles that can be used for disease diagnosis or therapeutic delivery. Our bodies are made up of billions of cells that coalesce into a wide array of interactive tissues. To co-ordinate activities within and between our different tissue types, we have evolved a variety of inter-cellular communication networks. Some simple interactions are controlled by single, small molecules called hormones whereas more complex messages require sophisticated transfer of information packages using "subcellular nanoparticles or biovesicles" that are jettisoned from one cell and selectively taken up by a distant recipient cell. During normal human growth and development, biovesicles play a key role in ferrying multiple forms of genetic information between cells and tissues within the body. There is now world-wide scientific evidence to support the notion that we can engineer and use biovesicles as nanomedicines to carry therapeutic information for the treatment of a wide spectrum of human diseases, including cancers. Our team has developed a novel therapeutic platform for producing therapeutic biovesicles in situ in the tumour niche. In this section, we will discuss our strategy to "hack" into the natural communication system used by biovesicles to transmit therapeutic information between cells and promote effective anti-tumour immunity.

Speakers

Carolina Ilkow
Eva Villalba
Abera Surendran

Schedule (all times in EST)

1:30 - 2:00 pm - HQP & patient perspective talks
2:00 - 3:00 pm - talk from Dr. Carolina Ilkow (The Ottawa Hospital Research Institute)
3:00 - 3:15 pm - plain language Q&A
3:15 pm session end

You can read more about this research project here:

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Session Four: Back to top

Therapeutic inducers of Natural Killer cell killing (ThINKK) : a novel approach to prevent cancer relapses after hematopoietic stem cell transplantation
Date: Thursday, February 4, 2021 | 1:30 - 3:15pm EST

As a pediatric hematologist-oncologist, I am keenly aware that some children with leukemia can only be cured by hematopoietic stem cell transplantation, more commonly known as a bone marrow transplant. As a stem cell transplanter, I painfully know that almost half of these transplanted children will ultimately suffer from leukemia relapse and die from their disease. As an immunologist, I also know that after the transplant, the patient's immune system is rebuilt from the graft stem cell. Scientific research shows that two components of this new immune system can help cure the disease by directly killing leukemia cells: T cells and Natural Killer (NK) cells. Unlike NK cells, T cells can attack the patient's normal tissues. This transplant side-effect is known as Graft-versus-Host Disease. It can lead to the patient's death.

The central idea of our research is that proper activation of graft-derived NK cells will prevent leukemia relapse. Indeed, data shows that activating these NK cells can cure leukemia.

We gave interferon-alpha, an NK-cell-activating protein, to post-transplant children with early signs of recurring leukemia and observed leukemia disappearance in some of them. But this effect is weak and inconsistent. However, natural activation of NK cells is not induced by a single protein, but rather by rare and specialized cells producing a vast array of proteins. These cells are called "plasmacytoid dendritic cells", or "pDCs". Therefore, we investigated how we could use these pDCs to activate post-transplant NK cells against leukemia.

Despite the common belief that lymphoblastic leukemia is resistant to NK cells, we demonstrated that pDCs were able to stimulate NK cells to kill lymphoblastic leukemia. We found that pDCs were absent or inactive in patients up to one year after transplantation, whereas NK cells were present and fully functional as early as six weeks after transplant. We set up a preclinical mouse model to simulate what happens in patients when they receive a transplantation. In this model, we showed that human pDCs were able to activate human NK cells to eradicate human leukemia.

However, there are two hurdles with pDCs. First, they are so rare that they cannot be extracted from humans for therapeutic usage. Thus, we devised a method to produce them from stem cells in sufficient numbers to treat patients. Second, some of the pDCs, and particularly a subtype called "AXL+", can activate T cells, and this can lead to lethal Graft-versus-Host Disease. As a result, we investigated the cells we grew from stem cells and discovered that they harbor very few AXL+ cells, that they did not activate T cells, and neither did they cause Graft-versus-Host Disease, in a preclinical mouse model. As their activating properties are restricted to NK cells, we named our cells "Therapeutic Inducers of NK cell killing", or "ThINKK".

ThINKK are not rejected by T cells, allowing us to grow them from a third-party stem cell source, with no relation to the transplant donor or recipient. ThINKK's activity is not reduced by most of the immunosuppressants used in patients after transplantation. They can be cryopreserved without losing their biological properties, which means they can be used as an "off-the-shelf product". We defined the optimal dosage and administration schedule in our preclinical mouse model.

With these data in hand, the next steps are to scale-up the production to "Good Manufacturing Process" grade, and to confirm the absence of toxicity of ThINNK in a setting accepted by regulators such as Health Canada and the US Food and Drugs Administration. We will then be able to proceed to the clinical trial.

Speakers

Michel Duval
Marie-France Langlet
Nicolas Poirier

Schedule (all times in EST)

1:30 - 2:00 pm - HQP & patient perspective talks
2:00 - 3:00 pm - talk from Dr. Michel Duval (Université de Montréal/ CHU Sainte-Justine)
3:00 - 3:15 pm - plain language Q&A
3:15 pm session end

You can read more about this research project here:

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Session Three: Back to top

COV-IMMUNO - A randomized, phase III trial of vaccination with IMM-101 versus observation for the prevention of severe COVID-19 related infections in cancer patients at increased risk of exposure
Date: Wednesday, January 13, 2021 | 1:45 - 3:15pm EST

The COVID-19 pandemic is a harsh reminder not to take our immune system for granted. The fact that some infected individuals clear the virus without symptoms contrasts with the damage that this virus does in more vulnerable populations, including cancer patients. The difference in severity is due to a number of factors, but most important is how well the innate arm of our immune system functions. Innate immunity provides a rapid, broad response and has been shown to be important in reducing the severity of many viral infections, including SARS and COVID-19. Patients who are receiving anti-cancer therapy are known to have suppressed immune systems, including poorer functioning innate immunity. However, there is evidence that the innate immune system can be boosted by vaccination against one infection to respond better to different infections, which is called "trained immunity".

The BCG vaccine against tuberculosis, which has been shown to train the innate immune system and protect against other infections, is also being tested against COVID-19 in health care workers but, because it is a live vaccine, it is not safe in immunosuppressed patients, like those with cancer.

We propose to use a new vaccine, IMM101, to train the immune system of vulnerable cancer patients. IMM-101 is a heat-killed vaccine so it is safe to use in cancer patients. We are therefore undertaking a clinical trial that will enroll 1500 cancer patients from across Canada who are at high risk of COVID-19 since they cannot self-isolate because they have to go to the cancer center to receive anti-cancer therapy.

The patients will be randomly assigned to receive either IMM-101 or to simply be observed over the course of their cancer therapy. If patients who receive IMM-101 suffer fewer and/or less severe respiratory infections, including COVID-19, compared to unvaccinated patients, there will be strong evidence to adopt this as a standard therapy for these patients, both in Canada and internationally.

Speakers

Rebecca Auer
Chris O'Callaghan
Judy Needham

Schedule (all times in EST)

1:45 - 2:00 pm - plain language summary by Judy Needham
2:00 - 3:00 pm - talks by Drs. Auer and O'Callaghan
3:00 - 3:15 pm - plain language Q&A
3:15 pm session end

You can read more about this research project here:

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Session Two: Back to top

Developing better CAR T-Cell Therapies by engaging patients, performing systematic reviews and assessing real-world and economic evidence
Wednesday, December 9, 1:30 pm – 3:15pm EST

Chimeric Antigen Receptor T-cell (CAR-T) therapy is a personalized immunotherapy, currently being assessed in a Canadian Phase I/II clinical trial to test safety and feasibility for relapsed/refractory blood cancer (CD19+ Acute Lymphoblastic Leukemia and non-Hodgkin's Lymphoma). This virtual seminar will provide an overview of a multidisciplinary team's collaborative efforts to synthesize evidence for the development of this clinical trial protocol, using a novel approach (the ‘Excelerator' model). This approach involved the completion of a systematic review (objective review of existing trial data), engagement of patients and clinicians, and drawing from real world and economic evidence. Dr. Fergusson will provide a brief introduction. Dr. Kednapa Thavorn will discuss the team's use of economic modelling to select trial factors to maximize economic feasibility of the therapy, and Mackenzie Wilson (HQP) will discuss the current efforts and future directions to engage diverse stakeholders to inform this work. Gisell Castillo (HQP) will speak about the interviews that were conducted with patients and hematologists to identify potential barriers and enablers to participation and recruitment to the trial. The team will also discuss two ongoing projects which build on this work. Dr. Lalu will provide an overview on the team's patient engagement program throughout development of the trial protocol and plans to expand this program to other immunotherapy trials. Joshua Montroy (HQP) will also discuss ongoing work building on the initial systematic review, to use individual participant data meta-analysis to identify factors that may impact the efficacy of CAR-T cell therapy. Dr. Justin Presseau will moderate the question and answer period.

Speakers

Dean Fergusson
Kednapa Thavorn
Mackenzie Wilson
Gisell Castillo
Manoj Lalu
Joshua Montroy
Justin Presseau
Madison Foster
Terry Hawrysh

Schedule (all times in EST)

1:30 pm - Plain language talk summary from Madison Foster (Clinical Research Assistant, OHRI, supervised by Drs. Dean Fergusson and Manoj Lalu). Terry Hawrysh will present the patient perspective.
2:00 pm - Introduction, Dr. Dean Fergusson
2:05 pm - Involving patients, healthcare providers, and health system stakeholders in an early economic evaluation of Chimeric Antigen Receptor T-cell therapy, Dr. Kednapa Thavorn and Mackenzie Wilson (Clinical Research Assistant, OHRI, supervised by Dr. Justin Presseau)
2:15 pm - Cautious Hope in the Face of Uncertainty: Identifying barriers and enablers to recruiting to, and participating in, an early phase CART cell therapy trial, Gisell Castillo (Research Coordinator, OHRI, supervised by Dr. Justin Presseau)
2:25 pm - MARVEL project, Dr. Manoj Lalu
2:37 pm - Individual Participant Data Meta-Analysis, Joshua Montroy (Clinical Research Associate, OHRI, supervised by Drs. Manoj Lalu, Dean Fergusson)
2:45 pm - Q & A Session, Dr. Justin Presseau
2:55 pm - Wrap-up, Dr. Megan Mahoney
3:00 pm - Plain language Q & A, Madison Foster and Terry Hawrysh
3:15 pm - Session end

You can read more about these research projects here:

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Session One: Back to top

Building a Trans-Canada Railway for CAR T-Cell Therapies
Monday, November 16, 2020, starting at 1:45pm EST / 10:45am PST

Chimeric Antigen Receptor T-cell (CAR T) therapy is a powerful tool for treating hematologic cancers and has begun to provide hope to patients without other therapeutic options to treat and cure their disease. This session, "Building a trans-Canada railway for CAR T-cell therapies," will include talks by four speakers who are members of a collaborative effort to enable the development of Canadian capacity for point-of-care CAR T-cell manufacturing. Dr. Natasha Kekre will speak about the development of the flagship ‘made-in-Canada' CD19 CAR T phase 1 clinical trial. Dr. Brad Nelson will discuss the development and manufacture of CAR T therapies and ensuing infrastructure and capacity development that will pave the way to enable more Canadian patients to access this new technology. Dr. Kevin Hay will present research on the development of a CD22 CAR, and Dr. Scott McComb will discuss future steps, including the development of a multi-targeted CARs, broader application of CARs to solid tumours, and other disease indications.

Learn more about CAR T in Canada

Speakers

Natasha Kekre

Dr. Natasha Kekre

Where we started: CLIC-01 CAR T clinical trial

Brad Nelson

Dr. Brad Nelson

Where we are: Point-of-care manufacturing

Kevin Hay

Dr. Kevin Hay

Where we are going next: Development of CD22 CAR T

Scott McComb

Dr. Scott McComb

What the future holds: novel CAR T design

Terry Hawrysh

Terry Hawrysh

Plain Language Summary Facilitator

Julian Smazynski

Julian Smazynski

Plain Language Facilitator

Natasha Kekre
Dr. Natasha Kekre
Where we started: CLIC-01 CAR T clinical trial
Brad Nelson
Dr. Brad Nelson
Where we are: Point-of-care manufacturing
Kevin Hay
Dr. Kevin Hay
Where we are going next: Development of CD22 CAR T
Scott McComb
Dr. Scott McComb
What the future holds: novel CAR T design

Schedule (all times in EST)

1:45 pm - Julian Smazynski, PhD student with Dr. Brad Nelson, BCCA will provide a plain language overview of the talks. Terry Hawrysh will provide a plain language overview of the talks from a patient perspective.
2:00 pm - Talks by Drs. Natasha Kekre (OHRI), Brad Nelson (BCCA), Kevin Hay (BCCA) and Scott McComb (National Research Council of Canada)
3:00 pm - Q&A from plain language audience with Terry Hawrysh and Julian Smazynski
3:15 pm - Session end

You can read more about these research projects and biomanufacturing facilities here:

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