In this episode we cover several important and related topics, including: the importance of pre-existing Immunity and novel ways to activate the immune system through Cancer Vaccines, Cytokines, Immune Agonists & T cell bispecifics.
The majority of these interviews were recorded at the American Society of Clinical Oncology (ASCO) meeting held in Chicago in June 2017, while others were recorded in Paris or at the Society for Immunotherapy of Cancer (SITC) meeting in National Harbor, MD.
Dr Jérôme Galon (INSERM) is a leading immunologist who works for the French NIH and is co-founder of a diagnostic company, HalioDx.
He has published some wonderful research over the last 15 years, including showing how the type, density, and location of immune cells within human colorectal tumors predict clinical outcome (Link) and how spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer (Link).
Dr Galon also developed the Immunoscore and Halioseek tests to help identify which patients colon and lung cancer respectively, are more likely to respond to immunotherapy.
He published some interesting work with Kite Pharma at ASCO this year, evaluating pre-existing immunity with their CAR T cell therapy, axi-cel (Abstract # 3025), which he discusses.
In this episode Dr Galon talks about what pre-existing immunity is, how it is measured and how it can be applied to the clinic.
For years we have seen many cancer vaccines come in to the clinic and subsequently go off to dog drug heaven with their tail between their legs.
In fact, with only one cancer vaccine ever approved by the FDA as an anti-cancer therapeutic (as opposed to a preventative therapy), the field has many sceptics. Despite this, it is also an area of opportunity for companies who are exploring innovative approaches in the clinic. Here’s one worthy example we wanted to highlight…
Dr Carlos Paya (Immune Design) is a former physician-scientist who is now CEO of a west coast cancer immunotherapy company.
He talks about their novel cancer vaccine (ASCO Abstract # 11006), which targets the cancer testis antigen NY-ESO-1 in soft tissue sarcomas. When given in combination with the anti-PD-L1 antibody, atezolizumab, they hope to increase the prime-boost effect thereby making the checkpoint therapy more effective.
The basic idea behind this approach is to activate the immune system’s natural ability to create more tumour-specific cytotoxic T cells to help the body kill the cancer cells.
In this episode, Dr Paya discusses the initial results with the combination and explains why some patients responded and others did not.
Update: Merck acquired Immune Design for $300M in February 2019 (News Release).
Cytokines are cell signalling molecules that are secreted by certain cells of the immune system and have an effect on other cells. They are proteins, peptides or glycoproteins and include the interleukins, interferons and other relevant growth factors.
They received much attention in the 80s and 90s, then were largely forgotten as other approaches gained more favour. Sometimes in science what was old is new again, and they may be making a comeback with a modern twist.
In this episode, he discusses what cytokines are, what they do and why they may be important in the context of combination approaches.
They discuss a investigative compound in early clinical development against CD122, which enables fresh cytotoxic T cells and natural killer (NK) cell populations to be stimulated, thereby boosting the performance of checkpoint blockade (ASCO Abstracts # 2545 and e14040)
We’ve heard in previous shows that the more tumour-infiltrating lymphocytes (TILs) present in the tumour(s), the more likely we are to get a sustained immune response.
Obviously this is great for patients who have those key cells already present, but just maybe we can also help people who are lacking the right immune cells with this innovative approach.
The duo describe the rationale behind their novel approach, explain the kind of biological effects they saw on the immune cells and what this means.
T cell bispecifics
Another way to attract more T cells into the tumour is to simply redirect them in.
Here, we interviewed a trio of researchers from Roche and Genentech, including a translational physician-scientist (Dr Friedrich Finckenstein), head of product development (Dr Dietmar Berger), and an immunologist-oncologist (Dr Dan Chen @DanChenMDPhD).
This innovative antibody approach could prove to be handy in converting noninflamed tumours into inflamed ones, thereby making checkpoint immunotherapy more effective.
They explain what a T cell bispecific is, how it works, and why they’re excited about this new approach, especially in cold tumours such as colon cancer.
Update: Since this interview all three have moved on. Dr Berger joined Sanofi as Head of Development in May 2019. Dr Chen is now Chief Medical Officer (CMO) at IGM Biosciences and Dr Finckenstein became CMO of Iovance Biotherapeutics in July 2019.
Pictured below are two of the Roche scientists who are co-authors of the CEA CD3 TCB poster (ASCO17 Abstract 2549), which Dr Chen discussed in the ASCO poster hall. The clinical data was presented by Dr Josep Tabernero (Abstract # 3002)
Additional References mentioned on the show
Pagès F, Berger A, Camus M, Sanchez-Cabo F, Costes A, Molidor R, Mlecnik B, Kirilovsky A, Nilsson M, Damotte D, Meatchi T, Bruneval P, Cugnenc PH, Trajanoski Z, Fridman WH, Galon J. (2006) Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med. Dec 22;353(25):2654–66. DOI: 10.1056/NEJMoa051424
Galon J, Angell HK, Bedognetti D, Marincola FM. (2013) The continuum of cancer immunosurveillance: prognostic, predictive, and mechanistic signatures. Immunity. 2013 Jul 25;39(1):11–26. doi: 10.1016/j.immuni.2013.07.008
Bindea G, Mlecnik B, Tosolini M, Kirilovsky A, Waldner M, Obenauf AC, Angell H, Fredriksen T, Lafontaine L, Berger A, Bruneval P, Fridman WH, Becker C, Pagès F, Speicher MR, Trajanoski Z, Galon J. (2013) Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer. Immunity. Oct 17;39(4):782–95. doi: 10.1016/j.immuni.2013.10.003
Bacac M, Fauti T, Sam J, et al. A novel carcinoembryonic antigen T-cell bispecific antibody (CEA TCB) for the treatment of solid tumors. Clin Cancer Res. 2016;22:3286-3297. PMID: 26861458
Lehmann S, Perera R, Grimm HP, et al. In vivo fluorescence imaging of the activity of CEA TCB, a novel T-cell bispecific antibody, reveals highly specific tumor targeting and fast induction of T-cell–mediated tumor killing. Clin Cancer Res. 2016;22:4417-4427. PMID: 27117182
Genentech kindly sponsored this episode of the podcast. We’re grateful for their ongoing support!
Instead of reading a corporate message, for Genentech sponsored episodes, we usually do a mini-interview or vignette with a company scientist.
For this episode, however, we decided to try something different and included an extended segment on an important area of new product development in the Immuno-Oncology space, which includes perspectives from translational research, product development and clinical research.
The music in this episode is by David Schulman, from his album Quiet Life Motel.
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