Biotech Strategy Blog

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

Posts tagged ‘Immunometabolism’

For the final postcard in our 2020 summer mini-series on the potential of immunometabolism in oncology R&D, we’re taking an in-depth look at the ways in which metabolic programming can overcome immunosuppression in the tumour microenvironment (TME), as well as looking at additional novel ways in which the fitness of T cells can be impacted.

We’ve already covered glutaminase, arginine, p38 and others, yet there are other metabolic effects to consider too, as we discover in our latest expert interview.  In the penultimate postcard, we looked at mitochondrial phenotypes and how they can impact both mitochondrial and T cell fitness, which are important aspects in making adoptive cell therapy (ACT) based approaches such as TILs and CAR-T cell therapies more effective.

Deep thoughts on immunometabolism and how it can impact antitumour response

These themes show up yet again, but in a rather different context because T cell fitness can also impact immune checkpoint blockade, oncogenic targeting, as well as transcriptional and epigenetic approaches.

As much as we have been slowing building up the evidence during this series, in the finale it’s now time to kick up things up a notch or two and draw some unifying ideas together.

We accomplish this feat with a rising young star in this particular niche, Dr Ping-Chih Ho, who is at the University of Lausanne.

He kindly spoke to BSB about his pioneering and prolific research, some of the critical questions he has sought to answer, plus what he sees are important future directions to consider in metabolism research.

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

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This is the penultimate post in our mini-series looking at the potential of immunometabolism for cancer new product development. The initial plans for six posts ended up being revised with a seventh and final article based on an additional thought leader interview.

What’s the immunometabolism prize?

Like a series of postcards from our travels, the aim was to offer a flavor of different approaches in the field, some of which are already being translated and evaluated by biotech companies in clinical trials.

Along the way, like conversations on a journey, we spoke to several scientists working at the forefront of this research. As regular readers know we don’t just interview the ‘great and good’ – the established PI’s but in this series – we also spoke to some emerging up and coming researchers too. Each offered a unique personal perspective on different aspects of metabolism and its potential role in cancer research.

In today’s post, we share an interview with a young researcher working on a novel and intriguing approach, which could improve adoptive cell therapy.

We expect to hear a lot more about many of the immunometabolic strategies we’ve highlighted over the course of coming months, so this is a theme we will return to as new data emerges.

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The past year has seen hype and hope over targeting KRAS mutant cancers and many challenges still remain to be addressed. We’ve seen the emergence of selective G12C inhibitors, as well as others targeting SOS1:RAS upstream and even related pathways to address cross-talk such as SHP2 and ULK1, for example. The oncology R&D ecosystem is beginning to motor again as new competitors start entering the niche.

Riding the KRAS wave

To put things into broader perspective, however, despite all the positive news in lung cancer, consider the colorectal carcinoma data was less impressive than lung because of more complex, heterogeneous disease.

Meanwhile, Lilly recently announced the discontinuation of their selective G12C inhibitor, LY3499446, due to adverse toxicity, so clearly it is not all going to be plain sailing in this landscape!

Let’s also not forget the G12C mutation is not the only viable target in this context. People with advanced lung cancer can also present with one or more of several co-occurring mutations such as the serine/threonine kinase 11 gene (STK11) and kelch like ECH associated protein 1 gene (KEAP1), for example.

Unfortunately those presenting with both STK11 and KEAP1 mutations – independent of KRAS status – often have a poorer prognosis and there remains an unmet medical need for effective new treatments.

In this fourth postcard in our summer mini-series on the potential of immunometabolism for cancer immunotherapy, we’re taking a look at a novel way to target KRAS mutant lung cancer and, in particular, those with an STK11 and KEAP1 mutation who tend to do poorly on current therapies.

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What do T cells want?

In the third post in our summer mini-series on immunometabolism, we’re continuing our journey by taking a look at glutamine as a target, and in particular, the potential of glutaminase inhibitors.

Cancer cells compete with immune cells for glucose and glutamine in the tumor microenvironment, and if the cancer cell wins then immuno-surveillance and anti-tumour immune response can be diminished. Of interest, glutamine addiction is commonly seen in cultured cancer cells.

This begs a critical question – can we target glutamine therapeutically in patients, and if so, what happens?

In this article we highlight an expert interview with Dr Jeffrey Rathmell, who is Professor of Pathology, Microbiology and Immunology at Vanderbilt, where he directs the Vanderbilt Center for Immunobiology.

Dr Rathmell is at the forefront of research into T cell fuels such as glutamine and has published preclinical work on early compounds in this niche, including Calithera’s glutaminase inhibitor, CB-839, for example.

He kindly spoke to BSB after the AACR20 virtual annual meeting where he chaired a session on Metabolism and the Tumor Microenvironment.

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This is the second postcard in our mini-series on the emerging field of immunometabolism and the translational potential for cancer new product development.

Over the course of three weeks, we’ll be sharing six postcards from our journey, three of which are based around interviews with scientists at the forefront of research in this niche.

What did we learn about immunometabolism at AACR20?

In this latest post we’re taking a look at some of the signals at this year’s virtual AACR annual meeting, which as usual had a wealth of data on offer, offering as it does a window into the future of cancer drug development.

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

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It’s the dog days of summer in August, traditionally a time when many of us go on holiday and while that’s more challenging in the uncertain times of COVID-19, we at BSB are taking a break for the next three weeks as we recharge/renew for a busy autumn of virtual meetings.

We won’t be writing much about topical news or recent data for the next few weeks, but instead, while we’re taking time out we’ve prepared a six-part mini-series looking at immunometabolism and its potential for cancer immunotherapy.  We’ve run this kind of series every summer over the last couple of years and they’ve worked out rather well.

One of the things we did on Seasons 3 and 4 of the Novel Targets Podcast was to look at topics involving emerging areas of complex research, where we often didn’t know all the answers yet there were emerging data worthy of time and attention. Immunometabolism is certainly a topic which meets those criteria – it’s been on our list to do a deeper dive into for a while and here we are now, with some extended time to make the most of the opportunity to do it some justice.

We’re obviously dating ourselves in that we used to write letters or send postcards to friends and family from our holidays, this mini-series is very much in that style.

To be clear, this is not intended to be a comprehensive review of absolutely everything in the landscape, instead we’ll be reviewing some of the key concepts, showcasing important papers, and highlighting data at AACR20 that caught our attention. There will also be mention of a few emerging biotech companies in the field and for good measure we have three interviews with scientists at the forefront of research, which may have excellent translational potential to the clinic.

By the end of our three-week journey together, hopefully you’ll gain a greater understanding of the new product development potential for cancer immunometabolism and be better placed to put into context new data as it steadily emerges over the coming months.

In this first post, let’s set the scene by looking at immunometabolism and the role it plays in the fate, function, and fitness of T cells.

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

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