Biotech Strategy Blog

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

Posts tagged ‘immune suppression’

George Martin’s quote seems rather apt this morning as NextCure announced there was disappointing single agent activity with their Siglec–15 directed agent (NC318) in an ongoing phase 1/2 trial.

There were a couple of initial partial responses reported at SITC last year and now it may seem as if the wheels are falling off the wagon.

What can we learn from the latest update?

It turns out quite a bit…

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Not in San Diego – What we wanted to explore in this post was some nice examples of either creative thinking outside the box or where researchers have challenged existing dogma and revealed some intriguing or unexpected findings. These are all examples from talks or posters showcased yesterday during the second AACR virtual meeting…

We take a look at several quite different approaches, which may either turn out to be useful new agents in clinical development, new targets, or even some unexpected tweaks in clinical trial design based on emerging evidence on the biology side that may lead to a new understanding in an area where previous attempts failed to yield a positive result…

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We are living in exceptionally challenging times and our thoughts are very much with all those healthcare professionals at the front line in the battle against Covid–19.

For people living with cancer, particularly those who have stage IV disease, the stark reality – in the UK and even some States in the US – is an ICU bed may not be available if they come down with the severe form of the disease.

When it comes to cancer research most labs, with the exception of those working on Covid–19, are now closed, but there is still data coming out to keep us all going as we work from home. ASCO20 will be a virtual meeting this year, while AACR will likely have some virtual presentations later in April. There are also plenty of publications coming out in journals from work already completed.

In this post we’re looking at newly published research and one possible immunological link between inflammation related to cancer and certain infectious diseases.

Last week we spoke to Dr Kamal Khanna (@Kamal_M_Khanna), Associate Professor at NYU Langone about research from his lab, which has just been published in the journal Science Immunology.

Although science is important, what matters most in these exceptional times is making sure everyone comes through it safely. Dr Khanna kindly spoke to BSB under embargo on Wed 25th March, where we also spoke about the surreal experience going on around him as we asked, how are things going with you in New York?

“It’s crazy. This has become the epicenter now. It just moved so fast here from having no cases and everyone wondering what’s going on to just explosion. Lab is shutdown, unfortunately. They’re allowing one person to go in at one time, in my lab just to maintain mouse colonies and do very limited experiments.

They’re allowing us to do the Covid–19 experiments, which we started just a few days ago, but also in a limited fashion. Those are the things we’re doing right now is simply plaquing the virus, and we have a few strains and we’re just testing growing them and so. We’re getting some limited human samples, but probably that will explode now. Our hospital has the most amount of Covid patients, so much so that they just made a makeshift morgue with a tent, unfortunately, right next to where we are.

So that’s the reality of where we are right now and hoping that this will peak at some point, they’re predicting in about 2 to 3 weeks that it would reach its apex and then all the social distancing and things that we’ve been doing, hopefully that will start to bring some of the numbers down, that’s the hope.”

In this post we offer an extended interview with Dr Khanna where we explore possible immunological links between inflammation in relation to cancer and infectious diseases and how research from his lab could generate new insights into cancer, as well as some potential impacts for Covid–19.

If you’d like to read our latest in-depth expert interview on cancer-related topics, please do consider supporting independent science journalism in these challenging and exceptional times.

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The annual ASH Dash often ends up with crowds waiting for the poster halls to open up – a daily scene captured from ASH19

With coronavirus and COVID–19 pretty much dominating attention and space in the global news on a daily basis lately, I am vividly reminded that not too long ago in December we attended the annual meeting at ASH in Orlando to experience busy scenes like the one on the right…

Imagine those packed crowds now in the current context – it doesn’t bear thinking about!

Which is why all of the oncology conferences we had been planning to attend this year are one-by-one postponing or outright cancelling their events until next year. This is going to create a lot of challenges for companies in terms of data release and presentations, to be sure, but what matters more is reducing the risk of the infection spread in order to limit the risk of serious cases developing.

The good news is that we do have a huge backlog of oncology data – novel targets, new agents, and emerging companies – to write about and share with our audience. There’s always a silver lining to be had if you look carefully enough.

Here’s one such example – a novel cancer target, agents in development, and an emerging company to highlight too…

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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.

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We’re continuing our mini-series on cracking the ‘glyco-code’ with an interview with Dr Lieping Chen (Yale), one of the world’s leading cancer immunologists, someone who has taken basic science and translated it into a spin-off company, NextCure (NASDAQ: NXTC) and a new product (NC318) targeting Siglec-15 that’s already being evaluated in the clinic.

Will upregulation of Siglec-15 turn out to be key in some cancer patients?

What happens if you identify a novel target that is expressed in a subset of patients that’s key to resetting the immune response and overcoming the immuno-suppressive tumor microenvironment (TME)?

Not only that, but you can potentially use a biomarker to select the patients most likely to benefit from what we’re calling a ‘targeted immunotherapy’ that’s directed at overcoming a specific immune dysfunction or defect.

Think of it as like when you press the factory re-set button on your iPad or iPhone.

Over the course of the coming year, we expect to hear a lot more about the early clinical data for this novel approach so in this expert interview we’re talking to the founder about the science that’s propelling NextCure forward.

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MLK Memorial, Washington DC

We’re continuing our previews of the forthcoming 2017 annual meeting of the American Association for Cancer Research (AACR) in Washington DC with a look at an emerging pathway that may impact checkpoint therapy.

It’s an exciting time in cancer immunotherapy, although only a small minority of people have remarkable long-term durable responses and the reality is that most patients, even if they respond initially, end up relapsing at some point.

There’s still a lot to learn about cancer immunotherapy – we’re just scratching the surface of what’s possible.

At AACR17 we can expect to see insights on the direction the field is going. In this post we take a look at an emerging pathway, and some of the key presentations and posters that you should see if you are in DC for the meeting.

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