Biotech Strategy Blog

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

Posts tagged ‘Tregs’

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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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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Time to unlock some novel IO targets?

Continuing our latest four part mini-series, this one is on novel targets and agents and we now turn our attention to immuno-oncology in the last two articles pertaining to this particular topic.

You can read the first two articles on targeted therapies here and here.

For the avoidance of any doubt, this latest review is not about T cells, far from it.

Instead we cover six different areas, most of which are related or integrated in some shape of form.

There’s a lot of promising new science now coming out to help us better understand the underlying biology and also think out of the box about ways to enhance or improve on existing research.

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Casa Milà, Barcelona

One of the pleasures of going to international cancer immunotherapy conferences is the opportunity to meet great scientists such as Sergio Quezada, PhD. He’s a Professor of Cancer Immunology and Immunotherapy at University College London (UCL) Cancer Institute.

After his PhD, he joined the laboratory of Jim Allison at MSKCC in 2004, and as we heard from Nobel Laureate Sir Richard Roberts FRS on the last episode of the Novel Targets Podcast (Link), working in the laboratory of a future Nobel Laureate is one of his 10 tongue in cheek suggestions to improve your chances of winning a Nobel prize!

Professor Quezada kindly spoke to BSB last week at the European Association for Cancer Research (EACR) “Defense is the Best Attack” conference.

In Barcelona, we talked about the research done by his UCL group into regulatory T cells (Tregs) that led to the development of a novel first-in-class Treg depleting anti-CD25 antibody.

As Prof Quezada told BSB:

“This was the dream. It was basic biology, a big curiosity, lots of basic biology and being very stubborn and lots of luck. And now we have something that came out of PhD students and postdocs that some medic or nurse is gonna be injecting at the end of the year into a patient, so it’s really exciting. It’s really, really exciting!”

We enjoyed talking with Prof Quezada and appreciated the perspicacious insights he shared on where we’ve come from and where we may be going.

If you’d like to read more about the science and potential for this approach in cancer immunotherapy, subscribers can log-in to read our latest thought leader interview or you can click to gain access to BSB Premium Content.

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The latest company immunotherapy announcement is from Lilly and Nektar Therapeutics, for a strategic collaboration to co-develop NKTR–358, which targets the IL–2 receptor complex, thereby impacting regulatory T cells (Tregs). It is thought that this target may have particular relevance to autoimmune disorders and other chronic inflammatory conditions. This agreement involves an initial payment of $150 million, with the potential for up to $250 million in additional development and regulatory milestones.

Source: Nektar Therapeutics

Preclinical data on this novel compound was recently presented on July 10th at the World Congress of Inflammation.

We first spoke to Nektar at SITC in November, including an interview with one of their leading scientists (Dr Jonathan Zalevsky) together with the academic PI (Dr Adi Diab), and I’m delighted to say that the dynamic duo graciously agreed to a follow-up discussion at ASCO last month on the emerging IO pipeline.

In our current analysis and commentary on the IO pipeline, we also look briefly at the Lilly deal with NKTR–358 in autoimmune disease.

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The race to the be first to market in the United States with a CD19 directed CAR-T cell therapy is a bit like the America’s Cup Challenge Race Series – one boat/company is ahead and then another is ahead, it’s an ever changing and fluid situation…

Americas Cup Portsmouth

In this post, we’re looking at questions from subscribers – so what’s in the July BSB mailbag?

* CAR T Cell Therapy: Is the recent FDA hold – that came and went in record time, a setback to Juno? Who will win the CAR-T race to market in the United States? What is the market opportunity in Europe?
* Jounce/Celgene Deal: Celgene have a reputation for doing deals with innovative biotech companies, but then what? Is the Jounce deal a good one, or is it a value destroyer?

There are a few other questions in the mail bag, but the above gives you a flavour of some of the commentary in this post.

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One of the (many) highlights for me at the recent annual meeting of the American Association for Cancer Research (AACR) was a “Meet the Expert” session presented by Professor George Coukos.

Prof George Coukos AACR 2016

Prof George Coukos AACR 2016

Professor Coukos is Director of Oncology at the University Hospital of Lausanne and Director of the Ludwig Institute for Cancer Research in Switzerland.

Ovarian cancer is becoming a fascinating battleground for cancer immunotherapy, with multiple challenges that must be overcome before we see improvements in outcomes, especially for women advanced disease.

The interview with Prof Coukos is a follow-on to the one we did on advanced ovarian cancer and checkpoint blockade at ECCO 2015 in Vienna with Dr Nora Disis (Link).

If you missed it, you can still listen to highlights in Episode 7 of the Novel Targets Podcast (Link).

After his AACR presentation, Prof Coukos kindly spoke with BSB and in a wide ranging discussion, highlighted some of the innovative clinical trial strategies he is working on to move the cancer immunotherapy field forward in ovarian cancer.

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National Harbor, MD – the 2015 annual meeting of the Society for Immunotherapy of Cancer (SITC) kicked off today with a series of workshops, and mini-symposia before the main meeting starts on Friday.

It is currently glorious weather for Maryland in November, almost too nice to be indoors, which probably means it’s going to be a cold winter for those who live up North!

National Harbor MD

Of note this afternoon/evening at SITC 2015 was an International Symposium on Cancer Immunotherapy entitled “Today’s Innovators, Tomorrow’s Leaders.”

Organized in collaboration with the World Immunotherapy Council (WIC), the symposium showcased up and coming researchers, each of whom had an expenses paid trip to SITC to present their work before an audience that included many of the “great and good” in cancer immunotherapy.  It was useful learn from the questions being asked from the floor too, further adding to the value of the session.

Dr Bernard Fox SITC 2015

@BernardAFox introduces the International Cancer Symposium and acknowledges the vision behind it.

Dr Bernard A Fox (@BernardAFox), a past President of SITC, in his introduction acknowledged the vision behind it, and in particular, the contribution of Dr Nora Disis (@DrNDisis). Those of you who listen to Novel Targets Podcast heard her in the most recent show.

SITC WIC International SymposiumToday’s daily highlights post offers a few of my “take homes” from this afternoon. It doesn’t discuss unpublished data but some of the presenters went into more detail about posters they are presenting later this week which was interesting.

The symposium was highly enjoyable and well worth attending. Hopefully, it will be repeated at next year’s SITC annual meeting.

Tomorrow here in National Harbor, I’m looking forward to the workshop on new perspective for target antigens in the changing immunotherapy landscape. That will be the subject of tomorrow’s daily digest. Stay tuned!

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