Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘Cancer Immunotherapy’

A Voyage of Discovery

This is the first part of our latest mini-series, which takes a closer look at the potential of gamma delta (γδ) T cells for cancer immunotherapy.

Prof Adrian Hayday FRS

Prof Adrian Hayday FRS

In this post, we’re focusing at the voyage of discovery made by one of the pioneers in the field, Professor Adrian Hayday, FRS.

We’re living in a golden age of immunology. Basic research conducted over the past thirty years is beginning to pay dividends as it is translated into new cancer treatments that leverage the power of the immune system.

As things stand today, however, the majority of cancer patients do not respond to approved immunotherapies such as checkpoint blockade, either as single agents or in combination with chemotherapy. This means that we still have a long way to go to make these therapies an effective and widely available modality for the majority of cancer patients.

Despite the “hype and hope” surrounding the approval of two cell therapies based on CD19 directed CAR T cell therapies for certain types of blood cancers, there remain many challenges before more widespread use is likely. These include long term durability and persistence, overcoming antigen loss/immune escape, developing safe and effective allogeneic (off-the-shelf) treatments, as well as finding suitable targets for solid tumours.

The cellular therapy landscape is undoubtedly still emerging. While many companies have jumped on the CAR T cell bandwagon, others are looking at new and novel opportunities, one of which is the potential of unconventional lymphocytes, such as γδ T cells.

The Francis Crick Institute viewed from The British Library

The Francis Crick Institute viewed from The British Library

Someone who is a pioneer and leading researcher in the γδ T field is Professor Adrian Hayday. He’s a Senior Group Leader and Assistant Research Director at The Francis Crick Institute and has been the Kay Glendinning Professor of Immunobiology at King’s College London since 1998. He was elected a Fellow of the Royal Society (FRS) in 2016.

Prof Hayday kindly spoke to BSB about his γδ T cell research and the voyage of discovery that have taken him from basic biology to translation into a novel cancer immunotherapy.

What is the potential of γδ T cells for cancer immunotherapy?

BSB readers will, hopefully, have a clearer idea after reading our latest four part mini-series.

To learn more from our latest expert interview and get a heads up on our latest oncology insights, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

Book Review – L’Immunothérapie des cancers

The latest addition to the burgeoning list of books on the advent of cancer immunotherapy comes from two French immunologists, Éric Vivier and Marc Daëron.

The timing of the award of the 2018 Nobel Prize for physiology or medicine to Jim Allison and Tasuko Honjo, certainly seems to have acted as a catalyst for the publication of several books about the field.

There are a variety of ways to approach the cancer immunotherapy story, ranging from the personal portraits of researchers behind the science to narrative storytelling based on the “Hero’s journey” where the intrepid hero embarks on a quest, overcomes challenges or tests along the way and then finally emerges triumphant. One could certainly fit Jim Allison’s life and accomplishments into that mold.

We don’t normally review books on BSB, but were very curious to see how immunologists themselves would approach their specialist area and tell the cancer immunotherapy story. After all, everyone views the world through the lens of their own experiences and the bias that creates.

L’Immunothérapie des cancers, histoire d’une revolution médicale’ offers the reader a journey through the history of science.

Marc Daëron is a researcher at INSERM, the Institut Pasteur in Paris and Centre d’Immunologie de Marseille-Luminy (CIML). He’s also an associate member of the Institute for History and Philosophy of Science and Technology.

Prof Éric Vivier at 40th Anniversary of Centre d’Immunologie de Marseille-Luminy

BSB readers are already familiar with Éric Vivier (Twitter @EricVivier1) who is a Professor of Immunology at the University of Aix-Marseille and was previously Director of CIML.

An expert on innate lymphoid cells, natural killer cells and innate immunity, he’s also a co-founder of Innate Pharma and is currently the company’s Chief Scientific Officer (CSO).

If you want to hear them in person, the authors discussed their book on a recent France Inter talk show, which also includes a couple of patients doing well on immunotherapy phoning in.

Assuming you have a reasonable level of French, is L’Immunothérapie des cancers, histoire d’une revolution médicale well worth a read? Who is the audience? What did we make of the approach taken by two eminent immunologists?

To learn more from our latest biotech and oncology insights, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

Preview of CICON18 – Part 1

4th CRI-CIMT-EATI-AACR meeting in NYC

The next conference we plan on attending will be the 4th CRI-CIMT-EATI-AACR meeting in New York starting on Sun 30th Sept.

Having been to the 3rd annual event in Mainz meeting last Fall, I have to say it was absolutely fantastic and well organised, with plenty of researchers giving some excellent science based talks.  There was also a heavy focus on neoantigens and neoepitopes in the poster halls, making it a good place to learn from up and coming young European researchers keen to share and discuss their work.

To find out what’s in store this time around on US soil, we took a look at the program and came up with the first of our previews exploring some interesting topics…

To learn more from our latest assessment and get a heads up on our oncology insights, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

When oncogenic and immunogenic worlds collide…

This week I was fascinated (but not surprised) to learn an interesting snippet from an article in Forbes on Hal Barron and GSK by Matthew Herper. Herper wrote:

“David Schenkein, the chief executive of Agios Pharmaceuticals, worked for Barron at Genentech. He says he’s never worked with anyone who read more of the original scientific literature on a topic before making a decision.”

This should be a given yet… not everyone does that. Dr Scheinkein (whom we interviewed here) is no slouch either, so that’s quite a compliment.  By the way, for an alternative take on the R&D update, check out John Carroll’s article on Endpoints.

Revvin’ up our understanding of the immune system

It is, however, good to see some CMOs and CSOs reading extensively in the literature themselves rather than relying on summaries from project teams, although I highly recommend they should because it’s a great way to keep the brain revved up with new developments and also understand the field more intimately.

This is also one reason why we have regular Journal Club posts on BSB – to highlight important new developments that are worthy of attention and explain why they matter.

It is encouraging that quite a few of our subscribers are c-suite execs, including CEOs, CMOs, and CSOs who often send in links to papers they are curious for an independent perspective on.

It’s time for the latest look at some key research that may have practical impacts in numerous ways…

To learn more from our latest thought leader interview and get a heads up on our oncology insights, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

Under the hood – a look at important new cancer research

One of the challenges of the short whirlwind period between AACR and ASCO is that many new research papers get published and largely missed or forgotten about in the data tsunami that drops as people eagerly (and almost exclusively) focus on the new abstracts that are available.

This is a real shame since there were many really good pieces of research that were rich in knowledge that were published around then.  My reading pile heading into AACR was much larger than usual, and after wading through it all, it built up rapidly again heading into ASCO, never mind over 20,000 abstracts to consider between those two meetings!

Contemplating new data…

With this in mind, it’s time for a new Journal Club post – these are surprisingly popular on BSB, although on reflection the selections have tended to highlight either new targets and areas of therapeutic potential or offer explanations for some of the phenomena that we are seeing.

New developments often (but not aways) allow us to step back and see results from clinical trials with greater clarity.

With this in mind, here are our latest selections for the BSB Journal Club, all of which should prove to be a useful read…

To learn more from our latest ASCO highlights and get a heads up on our oncology insights, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

Update on cytokines as novel cancer immunotherapy

In this post, it’s time to put your thinking caps on and empty your minds of any pre-conceived bias in order to play the modern version of Star Trek tridimensional chess aka IO combination trials.

Gems from the Poster Halls

Here we weave now together some important themes and highlight intriguing ideas that at first seem dissimilar, but actually have much more in common than many realise.

Data from bone chillingly cold poster halls of conferences in the distant past can come back and reviewed afresh in the light of new developments. The seasoned observer discards neither these findings or thought leader snippets of insights within nor forgets them in an instant, as many do after the hum of instant live reactions passes.

With oncolytic viruses and cytokines being much in the news of late, what can we learn about where things are likely headed?

To get a heads up on our latest oncology insights and commentary including sentiments from though leaders, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

Can STING agonists promote cancer metastasis?

Can STING (stimulator of interferon genes) agonists promote cancer metastasis in some patients?

That’s the intriguing question posed by research published recently in the journal Nature by Dr Samuel Bakhoum @Samuel_Bakhoum and colleagues. (doi:10.1038/nature25432) who found that, “chromosomal unstable tumour cells co-opt chronic activation of innate immune pathways to spread to distant organs.”

Samuel F. Bakhoum, MD PhD is a Holman research fellow at Weill Cornell Medicine and a senior resident in radiation oncology at Memorial Sloan Kettering Cancer Center in New York. The joint first author of the Nature article is Bryan Ngo, a student in the Weill Cornell Graduate School of Medical Sciences. It’s impressive work from two early career researchers.

The paper raises several important questions that drug developers – several of whom already have STING agonists in the clinic – may need to carefully think about.  It is, however, important to point out that this data is preclinical, so we don’t yet know what may or may not happen in cancer patients.

We first heard about the data published in Bakhoum, Ngo et al’s Nature article, “Chromosomal instability drives metastasis through a cytosolic DNA response,” at last October’s excellent AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics meeting in Philadelphia.

What we learnt at #Targets17 was that chromosomal instability is linked to tumour metastasis through the STING pathway.

Readers of BSB will know that we’ve been covering activation of innate immunity through the STING pathway for several years now (See posts: “What we learnt at AACR about Aduro ADU-S100” and “Tom Gajewski takes the STING out of Cancer,” to name but a few.

So how do we reconcile the positive and encouraging data that has led to development of multiple STING agonists, several of which are now in the clinic, with the potential that there might be a harmful aspect to them?

There are some important subtleties and nuances around this critical issue and that is the essence of this post and what we sought to gain more insight into, beyond the obvious superficial answer that there could be harmful effects involved.

The Roman god Janus is depicted as having two faces – one looking to the future and the other to the past.

There are also two faces to cancer immunotherapy: It can be a force for good, we can harness our immune system in a way that results in a positive outcome – people with cancer live longer, some are even cured.  Alternatively, if we harness the immune system in a negative way it can also be a force for harm. 

We heard on the recent Novel Targets Podcast episode that while combination cancer immunotherapies can be effective in a subset of people, they can also lead to rip-roaring toxicities as well as unwanted auto-immune side effects, and in some cases, these can be fatal.  With multiple inhibitory and activating forces at place, cancer immunotherapy can tread a fine line balancing these out.

Dr Bakhoum kindly spoke to BSB about the translational and clinical implications of this latest research.

Given the potential impact of this research, we also sought additional commentary from experts active in STING research such as Jason Luke, MD FACP (@JasonLukeMD). He’s an Assistant Professor in the Department of Medicine at the University of Chicago and a Principal Investigator for early immunotherapy trials, including those with STING agonists.

BSB readers may recall we did an in-depth interview with him at AACR17 (See post: Overcoming Immunotherapy Resistance). This time around, he shared his perspective on Dr Bakhoum’s research and looked at the potential clinical implications.

Like Janus, does the STING pathway really have two faces to it?

Should companies with STING agonists be concerned or not?

To learn more and get a heads up on our latest thought leader interview, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

Going beyond PD-L1 expression as a immune biomarker

One of the things that I’ve heard repeatedly over the last year is that many researchers want a better biomarker of response for checkpoint therapies than PD-L1 expression by IHC.

National Harbor

Indeed, we could expand that statement more broadly to say that there’s a real need for a better predictive biomarker of response to any immunotherapy, since there are more approaches out there now and not just checkpoint blockade. Plus combinations are evolving, complicating things further.

Fair enough, but what’s happening in this space?  Anything, Bueller?

We’ve covered a few emerging ideas in the past, although they were based on retrospective analysis – usually with a small N – and remain to be validated in prospective clinical trials.

There’s quite a few groups now much more active in research in this space, from academia to industry.  This is a good time to take stock and look at some of the emerging technologies that might be making a splash later if the data pans out.

To learn more insights on this intriguing topic, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

Targeting Natural Killer Cells in Cancer Immunotherapy

Cancer immunotherapy has been very much focused on T cells of late, but perhaps we shouldn’t ignore the importance of the innate aspect of the immune system and how that might help generate cytolytic activity to help kill cancer cells.

Regular readers will know that we’ve been following the potential of Natural Killer (NK) cell therapy and targeting NK checkpoints.

Sculpture in Mainz

At the recent CRI-CIMT-EATI-AACR international cancer immunotherapy conference in Mainz, we spoke with a scientist active in NK cancer immunotherapy research.

Dr Nicholas Huntington (@Dr_Nick_Bikes) leads a laboratory at the Walter and Eliza Hall Institute (WEHI) of Medical Research in Melbourne, Australia.  He’s also co-founder of oNKo-innate, a startup company focused on developing innate immunotherapies.

After his presentation in Mainz, he kindly spoke to BSB about his NK cell research and its potential as a novel target for cancer immunotherapy.

Here’s a short excerpt from our discussion:

Subscribers can log-in to read our latest thought leader interview or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

Red and green flags in 1L NSCLC trials

Periodically, we post an analysis and look at a particular landscape and the leading competitors within. One area of rather intense interest that we have been following is the progress (or march might be more precise) of checkpoint blockade in previously untreated metastatic non-small cell lung cancer (1L NSCLC).

Our extensive reviews and discussions in this area have included a look at:

In addition, I last posted my recent predictions on this space in July this year and already quite a bit has happened since then!

With a bunch of other phase 3 trial readouts coming up over the next couple of months, it’s now time for another update on what to watch out for, what to expect and why some studies can be handicapped differently.

Subscribers can log-in to read our latest insights on lung cancer or you can gain access to BSB Premium Content.

This content is restricted to subscribers

error: Content is protected !!