Biotech Strategy Blog

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

Posts tagged ‘NK cells’

Challenges and Opportunities with NK cells for cancer therapeutics

After extensive – and at times, intensive – preclinical and clinical research on the adaptive immune system and how best to activate the cytolytic T cells in both hematological malignancies and solid tumours, attention is beginning to increase on the innate immune system. In particular, researchers are investigating how approaches in this realm can be incorporated into rational combinations with adaptive therapies, such that outcomes might be improved more than with either alone.

Human Natural Killer cell  Source: NIH

There are a number of ways to activate the innate immune system and direct dendritic or NK cells, for example. Some therapeutics seek to boost the responses via different innate sensing pathways such as cGAS/STING or CD47/SIRPα, for example, while others involve targeting stimulatory cytokines, chemokines, toll-like receptors (TLRs), etc through various agonist molecules.

There are also a myriad of vaccination strategies to consider involving neoantigens or neoepitopes, not to forget NK cell infusions, various NK CARs, bi/trispecifics and even checkpoint blockade of NK related targets.

These development have typically not received the same amount of attention as their T cell cousins, but it’s certainly an active and fertile area of research and one that we are likely to hear more about going forward as new developments start to make their mark.

In a world of ‘T cell chauvinists’ – to quote Dr Adi Diab (MD Anderson) – let’s not forget or ignore the humble NK cells, which also have cancer killing abilities.

Over the next three weeks, we have an extended mini-series focusing on NK cells rolling out with interviews and commentary from academia and biotechs alike across both sides of the pond. It promises to be an interesting and provocative ride with plenty of critical questions to pose and resolve along the journey.

So, hang onto your hats for the first part of the journey…

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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?

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Top 10 #ASH17 abstracts to watch out for

No ASH pre-conference coverage would be the same without a shout out to Dr John Leonard (Weill Cornell). For 10 days prior to the annual meeting he counts down each day with a lymphoma study that caught his attention and tags it #LeonardList. The first one went up yesterday:

Do follow Dr Leonard and his lymphoma selections on Twitter – there are usually surprising ones in the middle that are quirky or interesting that makes you stop and think more carefully.

Our #ASH17 series we have already covered aggressive lymphomas and also developmental therapeutics.

Atlantic Olympic Sculpture

Up next in our third ASH17 Preview, we take a broad look at the wealth of abstracts available and highlight ten key presentations, irrespective of tumour type, which readers should be watching out for.

Some of these ‘Champions’ may not be immediately obvious and include interesting preclinical findings, intriguing new products in development, as well as eagerly awaited mature data from recently approved therapies. It’s an eclectic mix, to be sure.

There are definitely some early trends and interesting new molecules emerging from company R&D pipelines that are worthy of further consideration in this year’s batch of abstracts.

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Nektar hits it out of the park at SITC 2017

We’re at a crossroads in the IO space, where much of the low hanging fruit has been already plucked and now we could be in limbo for the next 2–5 years while we wait to see which of the IO-IO or IO-other combos pan out as winners.

Part of the problem is that we don’t yet know all the potential mechanisms of resistance or immune escape involved, so imagine figuring out how best to optimally modulate the tumour microenvironment on top is going to be challenging – each tumour type is heterogeneous and highly complex.

In addition, the field has heavily skewed towards obsessing almost exclusively over T cells, which may or may not be a good thing.  There are alternative approaches that are starting to generate interest and results.

As Andrew Shepherd, the fictitious leader of the free world in the American President famously said:

“We have serious problems to solve, and we need serious people to solve them.”

One promising company in this space is Nektar Therapeutics.  At SITC this week they had some elegant and intriguing early data that combined an innate immunotherapy approach with checkpoint blockade.  We have been following their progress for a while now and it’s a great time for an update!

Dr Adi Diab NKTR-214 #SITC2017

Here we explore the data and have our latest expert interview that is not merely a couple of paragraphs long with a few platitudes or topline quotes… this is, quite frankly, a comprehensive review and strategic roadmap of what Nektar Therapeutics are doing in the IO space, why they are doing things a certain way, and where they are headed – in their own words…

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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:

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A look at Nektar Therapeutics immunotherapy pipeline

The latest company immunotherapy announcement is from Lilly and Nektar Therapeutics, for a strategic collaboration to co-develop NKTR–358, which targets the IL–2 receptor complex, thereby impacting regulatory T cells (Tregs). It is thought that this target may have particular relevance to autoimmune disorders and other chronic inflammatory conditions. This agreement involves an initial payment of $150 million, with the potential for up to $250 million in additional development and regulatory milestones.

Source: Nektar Therapeutics

Preclinical data on this novel compound was recently presented on July 10th at the World Congress of Inflammation.

We first spoke to Nektar at SITC in November, including an interview with one of their leading scientists (Dr Jonathan Zalevsky) together with the academic PI (Dr Adi Diab), and I’m delighted to say that the dynamic duo graciously agreed to a follow-up discussion at ASCO last month on the emerging IO pipeline.

In our current analysis and commentary on the IO pipeline, we also look briefly at the Lilly deal with NKTR–358 in autoimmune disease.

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Targeting Natural Killer Cells in AML

Cellular immunotherapy with Natural Killer (NK) cells is emerging as a potentially effective treatment option for older patients (more than 60 years of age) with Acute Myeloid Leukemia (AML).

AML remains a disease with high unmet medical need, particular for those patients who relapse and are ineligible for a stem cell transplant (SCT).

There’s considerable buzz around adoptive cellular therapy and, in particular, chimeric antigen receptor modified T cells (CAR T cells). It is important, however, to note that there are other approaches worthy of consideration. See post: Could a Novel Cell Therapy replace CAR T cell therapy?

Cancer immunotherapy targeting NK cells has already shown some early promising results in AML. We await the read out of the EFFIKIR trial data for lirilumab (Innate Pharma/BMS), an anti KIR (killer inhibitory receptor monoclonal antibody (See post: Innate Pharma at an Inflexion Point, an interview with Hervé Brailly).

357-cover-sourceRizwan Romee, Maximilian Rosario, Melissa Berrien-Elliott and colleagues at the Washington University School of Medicine in St Louis (@WUSTLmed) recently published the results of a clinical trial with a novel NK cell therapy: “Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia.”

The paper was published on 21 September, 2016 in Science Translational Medicine (link).

Melissa Berrien-Elliott, PhD. Photo Credit: Fehniger Laboratory, Washington University

To better understand the trial results and what they tell us about NK cell therapy in AML, BSB spoke with one of the joint first authors, Melissa Berrien-Elliot, PhD (pictured right) and senior author, Todd A Fehniger MD PhD, Associate Professor of Medicine at Washington University.

This post is part of our series on the innate immune system.

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Innate Pharma at an Inflexion Point: An interview with CEO Hervé Brailly

While in Marseille for the scientific meeting to celebrate the 40th anniversary of the Centre d’Immunologie de Marseille-Luminy (CIML), I had the pleasure to interview Hervé Brailly PhD, the CEO of Innate Pharma, a leading biotech company in the Marseille Immunopôle.

dr-herve-brailly-innate-pharma-ceo

Innate Pharma (@InnatePharma) was founded in 1999 by six immunologists: Hervé Brailly, Eric Vivier, Marc Bonneville, Alessandro Moretta, Jean-Jacques Fournié and Francois Romagné.

Yesterday’s blog post on “Why Target the Innate Immune System? An interview with Eric Vivier” sets the scene for today’s post.

Innate Pharma, as the name suggests, has pioneered targeting the innate immune system. The company has leveraged the research undertaken at CIML by Professor Vivier and others in the field of innate immunity.

Innate is leading the way in immuno-oncology by targeting checkpoint receptors on natural killer (NK) cells. In 2011 Innate signed a licensing deal with Bristol-Myers Squibb for the development and potential commercialization of lirilumab.

In a recent financial report (link to Sept 8 press release) the company announced that several clinical trials would read-out in the forthcoming months.

Without disclosing any material non-public information, Dr Brailly kindly spoke with BSB and talked about his vision for Innate, what data readouts we are expecting, and the inflexion point the company is now at.

This post was updated on Feb 6, 2017 with the announcement that the EFFIKIR AML trial failed to meet it’s primary endpoint.

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Why target the Innate Immune system? An interview with Eric Vivier

Eric Vivier, DVM PhD (@EricVivier1) is a leading French immunologist whose research has focused on understanding the innate immune system, and in particular, the role natural killer (NK) cells and innate lymphoid cells (ILC) play.

prof-eric-vivier

He is Director of the Centre d’Immunologie de Marseille-Luminy (CIML) and a Professor of Immunology at Aix-Marseille University.

In addition to his academic work, he also co-founded the biotech company Innate Pharma back in 1999. Through the company, he is actively involved in the translation of basic research into new cancer immunotherapy treatments.

New clinical data is eagerly expected for one of these, a first-in-class monoclonal antibody against KIR (lirilumab). It is in phase 2 clinical trials with Innate Pharma and Bristol Myers Squibb.

At the recent scientific meeting to celebrate 40 years of CIML (#CIML40), Professor Vivier kindly spoke to BSB about his research into innate immunity and the Marseille Immunopôle, for which he is also a co-founder.

It is an immunology cluster that brings together academic/clinical research with innovative biotech companies looking to bring new drugs and diagnostics to market.

This is the second post in our mini-series from the Marseille Immunopôle and CIML40. It also sets the scene for forthcoming posts on targeting the innate immune system, something you can expect to hear a lot more about in cancer immunotherapy.

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