Biotech Strategy Blog

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

Posts tagged ‘NK cells’

A high tide marker stands out on the beach, what stood out at ASGCT20 for you?

As Covid–19 continues to exert its impact on the cancer conference schedule, the good news is that it isn’t a total wrecking ball effect as organisations turn to virtual meetings to enable researchers to share their work.

Some of the events we have ‘attended’ this year have been prerecorded in advance, while others have taken the form of live events. Having listened to both, I can say they have advantages and disadvantages either way.

To me, it doesn’t really matter if you are flexible and appreciate the effort the scientists are making to show their wares.

This week it’s the turn of the American Society of Gene and Cell Therapy (ASGCT) to be in the spotlight with a truly ‘live’ meeting.

In the latest post, we focus on some key Gems from the Poster Halls…

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This week the conference cycle continues with the annual meeting of the American Society of Gene and Cell Therapy (ASGCT) (Twitter #ASGCT20).

Due to the ongoing travel challenges and need for social distancing as result of Covid–19, one key annual immunology meeting originally slated for this month was AAI in Honolulu, which was sadly cancelled. Fortunately, ASGCT is being held as a live virtual meeting instead, so do check it out if you have a keen interest in this field.

One area we’re hoping to learn more about at ASGCT20 is cell therapy using natural killer (NK) cells. It’s an exciting and emerging area, which is attracting a lot of interest of late.

Those following the NK cell space will no doubt have seen the recent announcement of the collaboration between Kite/Gilead and Melbourne based oNKo-innate, co-founded by Prof Nick Huntington (@Dr_Nick_Bikes) and Dr Jai Rautella (Link to PR).

Other NK focused companies in the news include the licensing by Avectas of the CAR-NK cell therapy from Galway based ONK Therapeutics, founded by Prof Mike O’Dwyer (@MichaelodwyerMD) (Link to PR).

It’s definitely an exciting time to be an NK cell biologist!

In our ongoing series of expert interviews, we caught up with Prof Huntington from Melbourne to talk about the potential of CAR-NK cell therapies.

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In the fourth part of our mini-series in novel targets and agents in development we turn to novel cell therapy approaches that are perhaps under the radar for many observers.

While these might seem bleak times during a pandemic, there’s always a silver lining somewhere

While much attention has been focused on antigen loss or downregulation of the target wih adoptive cell therapies, research continues to evaluate various solutions to the problem.

One obvious way is to develop dual CARs or target multiple antigen targets of relevance to the tumour type being investigated.

There are other potential solutions being looked at, both in preclinical animal models and in translational work using cells from people treated with HSCT or CAR T cell therapies.

Here, we look at an alternative immunotherapy approach, which with time may have utility in both hematologic malignancies, as well as solid tumours…

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Time to unlock some novel IO targets?

Continuing our latest four part mini-series, this one is on novel targets and agents and we now turn our attention to immuno-oncology in the last two articles pertaining to this particular topic.

You can read the first two articles on targeted therapies here and here.

For the avoidance of any doubt, this latest review is not about T cells, far from it.

Instead we cover six different areas, most of which are related or integrated in some shape of form.

There’s a lot of promising new science now coming out to help us better understand the underlying biology and also think out of the box about ways to enhance or improve on existing research.

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In our latest expert interview, we depart from the usual focus on one of two particular or narrow topics and indulge in a more wide ranging discussion to explore a variety of issues facing the IO field and look at them from the perspective of a researcher who is experienced in working with antibodies in various forms.

We cover a lot of ground from CAR-T cells to bispecifics to NK cells – while many people in industry may see these approaches as separate modalities in different niches, in the future we may well see a greater convergent and opportunities for regimens and combinations rather than a more nihilistic either/or approach.

I have long been fascinated with design of molecules and how different tweaks or enhancements can change the way something works – for better or worse. Just as we have learned much from immune agonists and their biphasic curves that result from constant stimulation (and ways to fix that too), so too will we see CARs, T cell engagers, and NK cell therapies adapt and improve in terms of how they are constructed.

Who better to talk about these changes and the learnings to be had lately than someone who has built and tested many antibodies for a living and is now running his own company?

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For today’s post, we’ve curated our individual highlights from the tsunami of data that flew thick and fast yesterday between science sessions, oral presentations and poster hall gems.

There were some pleasant surprises in the mix, to be sure, plus the weather brightened up immeasurably!

Yesterday’s lunch time ASH Dash was quieter than usual

Having whittled the number of trial highlights for review and critique down to thirteen key insights and learnings, what made our joint list?

To find out more, check out the post below!

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Increasingly we are seeing more research on the inflammatory status of the tumour microenvironment (TME) in recent years, not to mention the impact of cytokine and chemokine signalling pathways, and how they can be manipulated therapeutically.

There’s also a much wider range of novel immunotherapy approaches being evaluated such as checkpoints, CARs and vaccines with respect to both T and NK cell therapies. There are also a few other immune cells being targeted for developmental therapeutics.

As part of the ongoing CICON18 Preview series, we take a look at what’s in store and why the latest ten we’ve highlighted matter in the broader context of the evolving landscape…

For those who missed it, Part 1 can be found here.

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Continuing our NK cell series, we turn to a different area of work within this niche, namely how cytokines can help boost effectiveness of the clinical responses in hematologic malignancies through their impact on memory-like cells.

Spring is in the air!

This is an important aspect to consider bearing in mind that while NK cells can be useful in attacking cancer cells, they are also notoriously more fickle and less durable than their T cell cousins in sustaining cytlotic effects.

How can this be fixed? What therapeutic approaches might be potentially useful in addressing the problem?

To find out more, we spoke to a learned clinician-scientist involved in research in this arena to learn more about what he had to say and also discover why a molecule they are working on in early clinical development is starting to look quite promising.

The good news is that it may also have utility in solid tumours as well, through the effects that it induces.

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Dr Michael Caligiuri (City of Hope)

In the first of our extended thought leader interviews relating to the latest mini-series, we explore NK cell research through the lens of one of the experts in this niche.

This one is more of a convivial fireside chat than the usual interviews where we discuss data, latest readouts, development blowouts, or clinical trials etc.

So who’s in the spotlight this time around?

It’s none other than Dr Michael Caligiuri (City of Hope) who also happens to be the current President of AACR.

What’s cool is that he has been involved in NK cell research for a couple of decades and has seen a lot of changes in that time.  He’s also an engaging and humble researcher who had some interesting perspectives on where success in the future might lie with approaches in this niche.

So grab a cup of joe and settle down to learning an intriguing story…

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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 NK 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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