Biotech Strategy Blog

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

Posts tagged ‘immune checkpoint blockade’

Scaling the ramparts in Real Madrido

It feels slightly surreal to be writing about this year’s annual ESMO confab instead of attending in person in Madrid, Spain.

While much of the time and attention at ESMO is usually focused on the major phase 3 readouts from various clinical trials, we will be covering these during the meeting as they are presented to avoid repetition since many of the topline company trial results have already been announced.

In this year’s conference Preview series, I wanted to take a step back and explore early new product development in several forms:

  • Biomarkers and potential new ways of predicting outcomes in development
  • Emerging novel targets of interest
  • Developmental therapeutics – trials and tribulations

This initial review will tackle some important developments pertaining to various biomarkers of interest.

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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.

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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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Mainz, Germany: A grey and gloomy day by the river Rhine has been brightened up by the quality of science on display at the 2019 annual meeting of the Association for Cancer Immunotherapy (CIMT) (Twitter: #CIMT2019).

Dr Nicky McGranahan presenting at CIMT 2019

We were last here in Mainz 18 months ago for the EACR-CIMT-AACR Immuno-Oncology conference.

Cancer immunotherapy remains a work in progress, however.

What’s increasingly becoming more important is understanding the science, in particular finding answers to critical “why” questions that help us to not only understand the biology of cancer, but also why some people respond and others don’t.

In this post, we describe some of the key highlights and have penned some thoughts on some of the oral talks and posters presented today.

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The annual ASCO-SITC meeting (#ImmunoOnc19) was held in San Francisco this year and has come a long way from the inaugural event we attended in Orlando.

Finding the signals amongst the noise

In the original 2017 event, I vividly recall as stirring presentation from Dr Limo Chen on targeting CD38 in solid tumours, last year we wrote an update on GU cancers including the STING pathway.

What’s in store from San Francisco and how do we go about finding key signals from the noise?

Over the next two posts I’m going to focus on new findings in various approaches that either look interesting and worth watching, or where there are lessons that can be learned for future developments.

This time around, some of the highlights surprised even me…

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The latest addition to the burgeoning list of books on the advent of cancer immunotherapy comes from two French immunologists, Éric Vivier and Marc Daëron.

The timing of the award of the 2018 Nobel Prize for physiology or medicine to Jim Allison and Tasuko Honjo (captured on the last episode of the Novel Targets Podcast), certainly seems to have acted as a catalyst for the publication of several books about the field.

There are a variety of ways to approach the cancer immunotherapy story, ranging from the personal portraits of researchers behind the science to narrative storytelling based on the “Hero’s journey” where the intrepid hero embarks on a quest, overcomes challenges or tests along the way and then finally emerges triumphant. One could certainly fit Jim Allison’s life and accomplishments into that mold.

We don’t normally review books on BSB, but were very curious to see how immunologists themselves would approach their specialist area and tell the cancer immunotherapy story. After all, everyone views the world through the lens of their own experiences and the bias that creates.

L’Immunothérapie des cancers, histoire d’une revolution médicale’ offers the reader a journey through the history of science.

Marc Daëron is a researcher at INSERM, the Institut Pasteur in Paris and Centre d’Immunologie de Marseille-Luminy (CIML). He’s also an associate member of the Institute for History and Philosophy of Science and Technology.

Prof Éric Vivier at 40th Anniversary of Centre d’Immunologie de Marseille-Luminy

BSB readers are already familiar with Éric Vivier (Twitter @EricVivier1) who is a Professor of Immunology at the University of Aix-Marseille and was previously Director of CIML.

An expert on innate lymphoid cells, natural killer cells and innate immunity, he’s also a co-founder of Innate Pharma and is currently the company’s Chief Scientific Officer (CSO).

If you want to hear them in person, the authors discussed their book on a recent France Inter talk show, which also includes a couple of patients doing well on immunotherapy phoning in.

Assuming you have a reasonable level of French, is L’Immunothérapie des cancers, histoire d’une revolution médicale well worth a read? Who is the audience? What did we make of the approach taken by two eminent immunologists?

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For what seems the longest time, we have seen the battle in metastatic clear cell renal cell carcinoma (ccRCC) being focused on various anti-VEGF TKIs, whether against interferon, mTOR inhibitors, and even each other.

Lately, anti-PD(L)1 antibodies have also come on the scene – both as monotherapy and in different combinations – so are things set to change?

Will it be plaining sailing or are there hidden dangers ahead for the unwary?

Here, we take a look at the ever evolving landscape in RCC and explore the issues and challenges surrounding some of the novel combination readouts, including a look at the role immuno-oncology might play going forward.

Not surprisingly, there’s a lot to consider, discuss and think about…

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Prof Tom Powles GU18 Title SlideAt the 2018 ASCO Genitourinary Cancer Symposium, one of the standout keynote lectures was from Professor Tom Powles, Director of the Bart’s Cancer Cancer Center in London who talked about Immune checkpoint inhibitors in Urothelial Cancer: which one and why?”

We’ve been following the highs and lows around checkpoint inhibitors in bladder cancer for some time, so it was interesting to hear what Prof Powles had to say in San Francisco.

How does he see the landscape evolving for immune checkpoint inhibitors?

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At the inaugural event in Orlando last year, one of the highlights for me was learning how important CD38 might turn out to be as another immune checkpoint target in combination with other approaches.

This year the meeting moved to the west coast and was held in San Francisco, making it the third one this month after JPM18 and GI18. Indeed, the fourth such event is also rapidly coming up with ASCO GU next month!

So what did we learn this time around? Quite a lot it would seem.

While much of the clinical data of late associated with immune checkpoint blockade (ICB) has been in metastatic melanoma and non-small cell lung cancer (NSCLC), two other tumour types that have received increasing attention in the IO space have been clear cell renal carcinoma (ccRCC) and prostate cancer.

There were a few interesting new things we can learn here…

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