Biotech Strategy Blog

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

Posts tagged ‘transcription factors’

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…

To continue reading our latest highlights on oncology new product development including commentary and analysis BSB subscribers can log-in or you can click to access the content.

This content is restricted to subscribers

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.

To continue reading our latest highlights on oncology new product development including commentary and analysis BSB subscribers can log-in or you can click to access the content.

This content is restricted to subscribers

Every year post SITC we offer a critique and short reviews with a running scorecard of some of the emerging new developments, which captured our attention.

Time for some new directions?

When going through this process some years we barely managed to find half a dozen promising yet early gems – the good news is we have ten to share plus four additional ones to be covered in separate company interviews.

So what was interesting this year – and just as importantly – why was it intrguing, and what does it all mean?

The good news is there are some really creative and fresh ideas coming down the pike replacing others likely to fade away quietly to dog drug heaven…

To continue reading our latest highlights on oncology new product development including commentary and analysis BSB subscribers can log-in or you can click to access the content.

This content is restricted to subscribers

In part 2 of the highlights from day 1 of the EHA/EBMT CAR-T cell meeting, we take a look at some of the emerging science discussed during some of the sessions and how the research might help drive novel and innovative approaches forward in the future.

It can be scary jumping into the unknown!

We’ve heard much about all the phase 3 clinical trials in lymphomas and multiple myeloma of late, yet what about new research which is helping to inform and improve performance of new CAR constructs?

In this latest discussion, we highlight some of the promising scientific concepts, which are emerging and could end up being incorporated into new CAR-T cell therapies down the road in order to address and tackle some of the current weaknesses…

BSB subscribers can read our latest cancer conference coverage and commentary – you can either log-in or click to access.

This content is restricted to subscribers

We’re living in uncertain and challenging times as the coronavirus impacts healthcare providers around the world and puts them in the front line of exposure.

Meetings are being cancelled or postponed as companies and institutions batten down the hatches and restrict non-essential travel. Nobody wants their employees to bring back an infection, nor does anyone want to be stranded or quarantined in a far-flung place. I expect many hospitals will also want their staff to be readily available as the number of cases escalate in many countries.

We at BSB are also carefully considering our plans and which conferences in coming months we will attend in person, and expect it will be fewer than recent years. We’ve already cancelled attendance at a couple of international meetings and are actively considering whether we will cover others remotely too.

The worlds of oncology and the coronavirus are colliding in many ways, including on the scientific level too.

It turns out that key RNA transcription factors may have a role to play as therapeutic targets for both cancer and the coronavirus.

Science is very much about making connections. In this post, we’re taking a look at one transcription factor that could be a useful target in the context of both coronaviruses and oncology.

It’s time to look through an alternative window and see an entirely different perspective…

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

This content is restricted to subscribers

It has to be said that this is one of the most jam-packed ESMO schedules that I’ve seen in a while!

Usually one has a few sessions they are interested in and lots of ‘free’ time to conduct interviews. That is definitely not the case this year with even parallel sessions at the same time as the Presidential (plenary) symposia, making for some very hard choices that need to be made.

Barcelona

Immune suppression can take the form of many targets – just taking out one of them may not be enough

As we start to see a renewed focus evolve on how to make immunotherapy work in or help more patients, there has been much attention on what we can learn from the addition of chemotherapy, additional checkpoint targets, immune agonists, various innate targets from KIR and NK cell checkpoints to TLRs and STING, neoantigen and dendritic cell vaccines, a telephone directory of cytokines, oncolytic viruses, etc etc to name a few, all with varying degrees of success.

What about exploring the inhibitory factors that induce immune suppression?  If we can reduce the cloaking and hostile tumour microenvironment, would that lead to more effectiveness with checkpoint blockade?  Maybe, maybe not.

In principle, it’s a sound idea yet these factors are both broad and incredibly varied in scope as a topic as to seem overwhelming at first.  The good news is that there are some emerging targets and hints of activity to come that are slowly beginning to emerge, making ESMO a good place from which to take stock of some new early stage developments.

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

This content is restricted to subscribers

Yesterday we posted the first part of an extended interview with Professor Gerard Evan (Cambridge), where we discussed the oncogene MYC and what we have learned from his and others work in this emerging field.

It hard not to be in Cambridge and think of biology as anything but an seriously intellectual pursuit, and yet there are many lessons to be gained from a better understanding of why things do what they do – in both health and disease – if we are to even think about going about manipulating them therapeutically.

The river Cam in Cambridge earlier this year

Without much ado, here’s the second part of the interview with Prof Evan, where we channel our inner Socrates and focus on a lot of whys rather than hows.

We turn to discussing the biological principles around how MYC and KRAS behave in concert, what we do and don’t know about p53 as a tumour suppressor, plus a few other related topics of interest, including what happens to immune cells in their lung and pancreas cancer models.  There’s also the little secret of what Prof Evan describes as the ‘dark matter of cancer biology.’

I highly recommend reading the previous post before moving on to digesting this portion of our enlightening discussion…

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

This content is restricted to subscribers

In the initial parts of the broader story on MYC, we have covered a basic primer on the MYC oncogene, including a look at the key work from the labs of Dean Felsher in Stanford (liver model) and Gerard Evan in Cambridge (lung and pancreas models) to set the scene.

We also heard from Dr Jay Bradner at NIBR about his work wth bromodomains and PRC2 and how deep transcription factors might interact with the immune system.

A couple of years ago at AACR, Prof Evan gave a wonderful talk about his Myc model in a session on ‘Drugging the Undruggable’ and happened to put up a dramatic slide that really caught my attention – MYC and RAS drive out T cells – and I was thinking why, how do they do that? I wanted to know more about this effect because unless we understand how and why it happens, that maybe we can possibly go about tackling cold/non-inflamed tumours in a more informed way when these oncogenes are actively controlling and driving the tumour growth.

Cambridge, UK

For me, the logical next step in this ongoing story on understanding MYC is actually to explore the biology a bit further – what have we learned from animal experiments that might teach us some clues about where to start looking if we want to go about drugging something therapeutically that’s not in the normal kinase domain like many so called ‘druggable’ targets are?

To answer this question and many others, we travelled over 7,000 miles as a the crow flies and tracked down the great man himself in Cambridge UK.  We ended up with one of my all time favourite interviews that we’ve been privileged to hear at BSB…

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

This content is restricted to subscribers

We’re continuing our mini-series on the MYC oncogene and associated super-enhancers and transcription factors, with a look at some of the molecular mechanisms driving epigenetic accessibility and how they interact with the immune system. It turns out that the two appear to be inextricably linked.

Dr Jay Bradner (NIBR)

It’s an exciting and emerging area in oncology R&D as companies and researchers begin to leverage basic science with a convergence between scientific fields to drive new opportunities for therapeutic intervention in cancer.

Included in this post are excerpts from an interview with Dr Jay Bradner from the Novartis Institutes of Biomedical Research. He’s most well known for his academic research on chromatin and bromodomain fields. As Dr Bradner told me during our discussion:

“MYC has so many target genes that I would imagine one might find any number of immune factors as augmented in their expression by MYC.”

As always, we covered a lot of ground and dived into more detail. There’s also been a number of recent research papers published since our discussion that have shed more light on the topic.

This is the second post in our latest mini-series. If you’d liked to read this and our coverage from the forthcoming ESMO, SITC and ASH annual meetings, do sign up to keep up to date…

To learn more from our latest expert 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

Through the window of aiming at tough to hit targets – with new approaches will we soon see more than before?

One of my big dislikes in oncology is the tendency to describe certain areas of R&D with the characterisation around the popular media epithet, “Drugging the undruggable.”

When we think of ‘undruggable’ in oncology R&D the first three targets that many people think of are MYC, RAS and TP53.

Quite aside from the issue that implies we can do little or nothing for those patients unfortunately affected is that it results in a more closed mind, a bit like half empty versus half full; it’s only undruggable in the context of what has gone before us and offers little in the way of future possibilities that lie ahead of us.

The RAS pathway is a great example of this phenomenon.

For years it was considered undruggable and yet despite that we now we have several selective BRAF mutation inhibitors, plus some nice approaches now emerging against KRAS mutations such as G12C (e.g. Amgen, Mirati, Araxes/J&J) and G12D, plus let’s not forget the potential for tipifarnib against HRAS mutant squamous cell carcinoma of the head and neck (SCCHN). All of these have shown some nice preclinical promise with some (BRAFV600E) already approved by Health Authorities.

There are other tough targets to think about too, including MYC and TP53, but rather than consider them undruggable, I’d rather think it just takes a little bit of time (and a lot research) before we understand the underlying biology better in order to figure what we can optimally target.

With that thought in mind, we have a new five part mini-series to share focusing on MYC. It’s actually been three or four years in the making ever since I heard a wonderful talk on the topic about improved mouse models that allow us to interrogate the biology more profoundly in order to understand how things work.

Not all of the interviews were theoretical in nature – we also talked to a leading scientist in this area involved in a largely unheard of start-up/spinoff with the goal of developing new therapeutic approaches against hard to target oncogenic drivers.

Before we go there on our journey, however, we need to begin with some basic understanding to set the scene…

To learn more 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

error: Content is protected !!