One of the frequently cited conceptual frameworks in Cancer Immunotherapy is the Cancer Immunity Cycle developed by Drs Dan Chen and Ira Mellman from Genentech.
Ira Mellman and Dan Chen
As we heard Dan and Ira tell us on the Novel Targets Podcast recorded last year at #AACR16, the cancer immunity cycle doesn’t include all the elements that we now know impact the immune system and whether someone will have an immune response. The microbiome is one example that readily comes to mind.
To address this, Chen and Mellman have now published the next installment in the series in Nature:
“Elements of Cancer Immunity and the cancer-immune setpoint.”
The review paper published last month incorporates the latest research into a different framework that looks at the factors that influence what they call the ‘cancer-immune setpoint.’
Anyone involved with cancer immunotherapy knows how fast moving and dynamic the field is, something they draw attention to:
“The pace of cancer immunotherapy clinical studies is such that they have outstripped our progress in understanding the underlying science. However, this situation has created the opportunity to combine emerging scientific and clinical insights in a synergistic fashion that… will also provide guidance for the identification of new targets… and the crafting of a framework for making decisions on a personalized basis.”
Conceptual frameworks such as those proposed by Chen and Mellman will be of increasing importance as we try to make sense of the tsunami of cancer immunotherapy clinical trial data, including combinations, that is coming our way over the next 18 months.
During my recent visit to San Francisco for ASCO GI, I had the great pleasure to catch up with Daniel S. Chen, MD PhD, (Global Head of Cancer Immunotherapy Development, Genentech/Roche) and talk about his latest thoughts on how we should think about cancer immunotherapy.
In writing these review papers he told me:
“We look at this as an opportunity to really think about the field, and try to conceptualize what is happening.”
We also discussed their collaboration with Kite Pharma, something of relevance to conferences this week as we head off to BMT Tandem and the ASCO-SITC meeting.
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Two of the most intriguing developments in cancer research over the last 5 years have been checkpoint blockade and CAR T cell therapies. There’s no doubt that they work – in some patients – or that toxicities can be challenging to manage at times, but what has been very interesting to me has been physician reactions to the rise of immunotherapies.
There has been much noise about biomarkers, including whether they work or not in this niche, as well as how do we go about selecting patients for therapies and combinations?
Ultimately, immunotherapies will be no different from targeted therapies in that we need to better understand the underlying biology in order to move forward beyond the low hanging fruit and figure out how we can best select appropriate therapy for each individual based on their particular characteristics.
The worry that many researchers have is that we could end up making the same mistakes with immunotherapies as targeted therapies, i.e. treat them in a broad fashion akin to throwing mud at the wall. Indeed, some companies are already doing this, much to the consternation of the research community.
So how do we go about doing things better and thinking more strategically about what needs to be done?
Up next is the first in a two-part interview series with a global thought leader who is a scientist-clinician with expertise in both immunology and oncogenic pathways. What does he have to say about where we are now and importantly, what does the future hold?
This is the penultimate article in our coverage from the Triple meeting in Munich, held in November 2016.
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The Future of our (cancer research) Business
Happy New Year! No one really wants to spend too much time in the past dwelling on the negatives, what didn’t work, and in some spectacular cases, who’s to blame for it.
What we do want to know is what are the learnings from such endeavours and where are we going next.
Let’s look forward rather than backwards then and see what the Maverick’s crystal ball is showing in terms of fresh clarity and new trends we can learn from …
In today’s post I want to take a moment to look at some of the trends we can expect to see occuring in cancer research in 2017.
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This post started out as a look a one of the Gems from the Poster Halls at ESMO, including an interview with a thought leader in biomarkers, then morphed into a broader Op Ed that includes a strategic analysis of where we are, where we are going, and how we could get there more effectively and efficiently.
It’s time to turn tables to start challenging the status quo and slow pace of development if we really want to make a difference in advanced ovarian cancer. I was recently challenged by a well respected GYN oncologist to delineate how we could do things differently so here are some ideas, along with the scientific rationale in my response to his gauntlet.
Is the ideal situation one where multiple companies randomly throw mud at the wall hoping something sticks the best approach? Or are there more effective ways to make a difference?
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Copenhagen – it’s the end of Day 2 of the European Society for Medical Oncology (ESMO), which this year had a record-breaking 20,239 attendees.
Three of the presentations in today’s plenary Presidential Symposium were simultaneously published in The New England Journal of Medicine – I haven’t seen that happen before.
All three were also featured in this morning’s media briefing in Copenhagen.
- Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer (NEJM link)
- Prolonged Survival in Stage III Melanoma with ipilimumab Adjuvant Therapy (NEJM link)
- Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer (NEJM link)
In today’s daily digest there’s top-line commentary and insights from some of the sessions we attended. In a separate post, we have already discussed the niraparib data.
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Marseille – When it comes to biotech clusters for immunotherapy, Marseille, the second city of France, has to be right up there along with Boston, San Francisco in the United States and the “Golden Triangle” of Oxford, Cambridge and London in the UK.
I’m here in Marseille thanks to an invitation from Professor Eric Vivier to attend the 2-day scientific conference that the Centre d’Immunologie de Marseille-Luminy (CIML) have organized as part of their fortieth anniversary celebrations (1976-2016). It starts today (Twitter #CIML40).
Surrounding CIML in the picturesque national park (Parc National des Calanques), just outside the city, are innovative biotech companies focused on immunology and cancer immunotherapy. The combination of companies, research institutes and academic hospitals in the region has created the Marseille Immunopôle (@Immunopole). The area should already be on your radar if you are following the field.
Yesterday, I visited HalioDx (@HalioDx), a start-up company a stone’s throw from CIML. It was founded in 2015 to commercialize Immunoscore, a novel biomarker in colon cancer that can be used to stage patients based on their immune response.
Vincent Fert, CEO of HalioDx
We’ve been following the work of Dr Jérôme Galon on the blog for some time (see posts from European Cancer Congress 2015 and ASCO 2016), so it was a pleasure to talk to Vincent Fert, CEO (pictured right) and co-founder of HalioDx, about his plans to commercialize Immunoscore in Europe and the United States.
If you want to know more about the science behind Immunoscore, do listen to the recent Novel Targets Podcast (@TargetsPodcast) interview with Dr Galon, where he talks about the data he presented at ASCO 2016 (link to Episode 13: Immunotherapy or Bust).
The field of cancer immunotherapy is making rapid progress. It is already reaching the point where — in order to optimize the chance of a durable response — doctors need to know what a patient’s underlying immune response to cancer is, in order to direct therapy.
Vincent Fert and HalioDx are leading the way with the commercialization of a new diagnostic approach for colon cancer based on a patient’s immune profile. He kindly spoke with BSB about his plans for the company and making Immunoscore available in the US and Europe.
This is the first post in a mini-series from the Marseille Immunopôle.
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The ASCO Wall 2016
There has been much frustration on many fronts at the number of trials that do not see a relationship between PD-L1 expression and response. Some do, but many don’t. This has lead to quite a few investigators suggesting that the IHC assay may not be as useful as originally hoped, for predicting response to checkpoint blockade or selecting patients for therapy.
While we often do see a trend for more responders with higher levels of expression, the main issue is that PD-L1-negative patients can also see some responses, albeit at a lower rate.
There are many factors that can affect the measurement:
- Fresh vs. archival tissue
- Heterogeneity within the tumour
- Tumour cells (TC) vs. immune cells (IC)
- Different antibodies used for each assay
- The dynamic nature of the tumour microenvironment – does timing of the biopsy matter?
- Human error – a pathologist has to eyeball the IHC readouts and decide the level of staining intensity
And so on. These are just a few examples of the factors that can potentially affect the results, making it quite a challenging test to undertake. There is also time – does the level of expression vary temporally depending on which prior therapies are administered?
It would be easy to be disheartened by this, but fear not!
There were some impressive new data presented at ASCO that were not only intriguing, but also show us a way forward on how a multi-factorial approach could be used in different tumour types. By this I mean we might end up with different tests used in conjunction for several different cancers in order to a) predict responders and non-responders and b) better select patients for appropriate regimens or clinical trials.
It’s not going to be as easy as one size (or test) fits all. Sometimes a more more sophisticated approach will be needed. New data at ASCO gave us hints on what’s to come in this direction.
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We have selected five key strategic trends that are emerging that will be critical to follow, understand, and even implement if you are on the coal-face of clinical research and new product development.
We aren’t talking about financial things such as cost toxicity, or even how doctors should be paid, but meaty scientific aspects that we need to watch out for. If we are going to improve on cancer research and R&D in the future, these issues will be important.
For companies and academic researchers alike, there is much to learn from the tsunami of data that hit this week if you have a keen interest in the field and a bent for making sense of patterns out of an amorphous mass of data.
Not paying attention to evolution in clinical development can mean the difference between being in the winners circle, on the outside looking in, or falling way behind your competitors. Playing catch up is never anyone’s idea of fun in this market – oncology moves at a lightning fast pace compared to many other therapy areas.
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In our post AACR analysis, I noticed some consistent observations across multiple talks and informal discussions with thought leaders.
Some of these ideas are pretty important and help us see the big picture for the near and medium term future in the cancer immunotherapy space.
The “Claws” sign we saw at the University of New Orleans sums things up!
Without much ado, it seems a good point to capture and summarise these ideas so that readers can compare notes and debate their thoughts too.
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Biomarkers are a hotly debated topic at the moment within the cancer immunotherapy field.
At the recent Society for Immunotherapy of Cancer annual meeting (SITC 2015), there was even a debate with industry representatives arguing the “pros” and “cons.” Daniel Chen, MD PhD from Genentech (pictured right) argued “pro” and Steven Averbuch MD (pictured left) from BMS argued “con.”
The challenging question for anyone at the moment is if your Parent, Spouse or Best Friend were PD-L1 negative, would you still want them to receive a PD-1/PD-L1 checkpoint inhibitor (presuming it was indicated for the disease) and have a chance of a response, even if their PD-L1 negativity would suggest only a slim chance of responding?
AT SITC 2015 we spoke with an industry expert who offered insights into a leading company’s biomarker strategy and what the future may look like in 5-7 years time.
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