Biotech Strategy Blog

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

Posts tagged ‘T cell exhaustion’

Powering up CAR-T cells

Tackling T cell fitness and exhaustion will not be plain sailing, yet they will be an important focus going forward

One of the often ignored challenges in advanced cancers – regardless of whether they are hematologic malignancies or solid tumours – is the quality of the patient’s T cells.

Oftentimes these may be dysfunctional or exhausted, which means responses to any given therapy will be impacted in a negative fashion.

What if we learn more about the underlying biological processes involved – can the knowledge acquired lead to enhancements in the design of CAR-T cell products, the overall quality of the T cells, and hence improvements in outcomes?

While several companies have been active on this front, we went deeper and spoke with an academic researcher keen to leverage research findings, which may uncover novel approaches for future developments.

Rewriting T cells may prove to be an important emerging area of research to watch out for in 2024…

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Same Controller, Opposite Outcomes

Immune cells look and act differently

In this latest post from the American Society of Hematology meeting we explore some of the scientific data emerging from San Diego.

Specifically, we are looking at how transcription factors such as TOX2 can drive divergent fates in T and NK cells.

It might be tempting to think it sounds a bit dry, yet the findings could have important implications for future therapeutic developments – especially in the design of novel chimeric antigen receptor (CAR) cell therapies, an area where CAR-NK cells have constantly struggled with poor persistence.

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A look at T cell therapies at ASH23

Next stop – the ASH convention center!

In our final Preview ahead of the annual meeting of the American Society of Hematology (ASH), we’re focusing on immunotherapies.

With thousands of abstracts to wade through, it’s all too easy to think either there isn’t much going on or worse, so much it’s too complicated to even think about parsing.

To make things easier we picked ten different approaches to discuss, mostly involving early stage developments across numerous companies (big and small), plus a variety of targets, modalities and even immune cell subsets.

The value of looking at these kind of approaches now is being more prepared later in anticipating evolving trends and competitors because the IO space moves fast – and stealthily…

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A window into the future of IO

Phare de Kerkmorvan depuis 1849

It’s time to shine a light – or more correctly a beacon – on a novel approach to tackling advanced tumours.

If we want to improve beyond the low hanging fruit in immuno-oncology then we need to start tackling some of the more difficult challenges.

By the way, have you ever noticed how many observers will pick up on whatever is moving – like the sailboat in the photo – while missing the bigger picture that’s been around for a lot longer right in front of them?

Sometimes this happens in cancer research too.

Today’s story is very much along on these lines where an increasing body of research is starting to add up regarding an axis many have ignored, although admittedly it’s not as old as the lighthouse.

The thing is though, it could well turn out to be more enlightening than many realise…

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Tilting at windmills

Sometimes I wonder when we are faced with particularly difficult challenges in oncology – there are certainly plenty of these to go around – if people give up before they start and consider certain endeavours far too difficult and thus any emergent approaches are considered tilting at windmills.

What if we could isolate and define the problem more specifically, thereby identifying where new targets might lie and then go about designing ways to tackle them?

When we do this the problem at hand is much more specific and less amorphous.

Here, we highlight and explore a key topic likely to be lurking in many abstracts over the next week across both hematologic malignancies and solid tumours alike… it’s an important subject many will ignore at their peril.

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Leaves of grass

Fall leaves in Boston

Autumn (or Fall for our American readers) is a time of cyclical renewal as old leaves die off and fall by the wayside to make way for new growth to emerge.

It’s the same process in oncology R&D pipelines too; by 4th quarter earnings reports we start to see Product X or Y being officially discontinued/abandoned, or sent off silently to dog drug heaven without even an epitaph to claim.

What about the promised new growth opportunities or targets?

Well there are various cancer conferences either happening now or coming up, which should offer plenty of signals for hope amongst SITC, EBCC, SABCS, ESMO IO, with ASH signing off the final coverage of the year.

In our latest report, we highlight some key presentations to watch out for not covered in the earlier SITC previews.  Some look encouraging already, while others – in all fairness – may have some unexpected question marks to consider…

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The art and science of a novel immunotherapy for solid tumours

This week we have been following the latest preclinical early stage clinical data coming out of the EORTC-NCI-AACR ENA Triple meeting in the beautiful city of Barcelona in Spain.

One presentation in particular on the art and science of overcoming T cell exhaustion with an intriguing and novel immunotherapy approach caught our attention.

What’s special or different about this particular immunotherapy and why does it stand out from the increasingly very competitive IO crowd?

Curious to learn more?

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Revelations

Photo by Blue Ice Publishing LLC

The path to success with CAR-T cell therapies in solid tumours has been a long one with many challenges and barriers to overcome along the way.

Lately though we have started to see some initial hints of success, even in previously intractable cancers, which is both exciting and promising to see how the field is currently taking shape.

At the annual meeting of the American Association for Cancer Research this month we were encouraged by a number of talks focused on creative solutions to the problems faced as well as both inside and outside the box thinking.

If interested in learning more about the developments and where things are headed, check out our review of the opportunities and remaining obstacles to success,,,

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The paradox of immune cell populations and transcription factors

It’s interesting to me how people often think of science as absolutes or black and white, and yet paradoxically we consistently see more yin and yang effects, with the tipping point determined by context or the specific situations encountered.

In immunology, there’s also a fine line between too much and too little thus finding the threshold is a very tricky thing indeed.

For a long time I have been fascinated by what I call the hidden underbelly in immunology… we look at various inhibitory or stimulatory factors in response to a particular targeted therapy all the while ignoring the vast networks of transcription factors, which might offer some helpful context to any particular situation.

Often times, companies rush headlong into clinical trials without really paying attention to these details, some of which may exert effects not considered in the bigger picture and end up being surprised or blindsided down the road.

Here then, we explore some important recent research, which may well open quite a few people’s eyes and reconsider when is enough, enough – or even too much – and how does this line have a role to play in the immuno-oncology (IO) field?

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A different IO approach to tackling solid tumours

Time to consider new horizons in the IO niche?

Over the last five years or so we have seen how the immuno-oncology (IO) space has been transformed by both checkpoint blockade and CAR-T cell therapies in solid tumours and hematologic malignancies, respectively.

A raft of other targets are also being tested in various combinations to address additional inhibitory checkpoints, various immune agonists from cytokines, stimulatory checkpoints, TLRs and so on, as well as inhibitory factors inducing a more hostile tumour microenvironment.

What about the quality of the T cells at baseline?

The number of approaches seriously exploring this issue have been surprisingly few and far between, which creates new opportunities for companies seeking to take up this challenge.

In our latest expert interview series, we talk about the science around T cell dysfunction and what a young biotech are doing with some innovative ideas to address a common issue faced by many people with advanced cancer…

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