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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National Harbor, MD
With the abstract drop from the 2019 Society for the Immunotherapy of Cancer (SITC) meeting now available, what can we learn from some of the research slated for formal oral presentation this year?
Here in part one (posters will be reviewed tomorrow) we take a look at a mix of preclinical and early clinical studies that grabbed our initial interest from the oral presentations – they include the good, bad, and intriguing – to see exactly what can be learned from this year’s mix of abstracts?
The short answer is quite a lot.
Every year the what to watch out for preview is a popular one. This year there are some surprises in store as well as some particularly important findings that BSB readers may well be keen to find out more about ahead of the conference later this week in order to maximise their thinking and avoid the inevitable brain-fry and fatigue that sets in on Saturday afternoon…
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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.
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T lymphocyte Source: Dr Triche, NCI
It’s time for an update on cytokines as there is a lot going on here across both academia and industry.
While the clinical proof of concept has been demonstrated for IL-2 with FDA approval going back to 1992, there’s still much that we don’t know when it comes to the telephone directory containing many of the others.
There’s quite a few questions that can be asked:
- Which ones might be best in which tumour types?
- What about timing, dosing, and sequencing?
- Which early combinations look promising in terms of unleashing the T lymphocytes?
After all, let’s not forget that some cytokines will induce negative immunosuppression, while others might induce variable effects depending on what they encounter in the tumour microenvironment. It’s certainly a lot more complicated than many people truly realise.
There’s also the much under-rated potential to combine cytokines with other approaches such as immune agonists in order to jumpstart the colder tumours.
In this latest update, we take a look at five very different approaches and see how much progress is being made with alternative forms of immune modulation – the resulting conclusions might well surprise quite a few readers!
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In this post, it’s time to put your thinking caps on and empty your minds of any pre-conceived bias in order to play the modern version of Star Trek tridimensional chess aka IO combination trials.
Gems from the Poster Halls
Here we weave now together some important themes and highlight intriguing ideas that at first seem dissimilar, but actually have much more in common than many realise.
Data from bone chillingly cold poster halls of conferences in the distant past can come back and reviewed afresh in the light of new developments. The seasoned observer discards neither these findings or thought leader snippets of insights within nor forgets them in an instant, as many do after the hum of instant live reactions passes.
With oncolytic viruses and cytokines being much in the news of late, what can we learn about where things are likely headed?
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National Harbor, MD – Day 2 of #SITC17 brought some interesting highlights on a number of fronts, not all of which may be apparent at present, but there are a few readouts that will have a broader impact going forward.
SITC 2017 Stars?
As we move into an era where we see more combinations evolve in immuno-onology, things are likely to get more confusing rather than less so and it could well be another 3-5 years before things truly settle down and more concrete trends emerge.
Here, we reviewed 10 different areas of interest with a strong clinical relevance and explored the topics further.
Please note that some of these will also have follow-on posts with thought leader interviews and related poster reviews.
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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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Dr Mario Sznol at SITC 2015 Patient Forum
“Novel Immunotherapies and Combinations” was the title of the talk by Dr Mario Sznol (Yale) at the recent Immunotherapy Patient Forum co-hosted by Global Resource for Advancing Cancer Organization (GRACE) and the Melanoma Research Alliance at the 2015 SITC annual meeting.
At the forum, Dr Sznol also led a breakout session, where he reviewed what is melanoma, the treatment of primary melanoma and management of advanced disease, as well as answering questions from the patients and patient advocates.
Often at medical meetings you hear the results of a clinical trial that is but one piece of the jigsaw, so it was interesting to hear a more comprehensive overview of the disease.
Dr Sznol kindly spoke with BSB about his vision for the future of cancer immunotherapies. This post includes excerpts from the interview along with additional commentary.
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One thing has become very clear in the oncology space over the last year… checkpoint inhibitors are insufficient on their own for the vast majority of tumour types and patients that they have been explored in to date. There are a number of reasons for this, but the main one is lack of T cells in the tumour, which enable an effective immune response to be mounted.
This begs the question – how can we address that issue and manipulate the tumour microenvironment in our favour, thereby making subsequent checkpoint blockade more effective?
There are a number of different ways to do this.
In the past, we’ve discussed several methods including innate immunotherapies such as Aduro’s STING or Biothera’s immunotherapeutic, Imprime PGG. Other approaches include vaccines, which we have discussed in detail, t-cell receptors (TCR) or even monoclonal antibodies, such as AdaptImmune’s approach with their ImmTac technology.
There are other novel strategies currently being investigated by numerous companies too.
In this article – and also the second part of the latest miniseries – which will post tomorrow, we straddle our final reviews of interesting data from the European Cancer Conference (ECC) in Vienna with the upcoming one from the Society of Immunotherapy for Cancer (SITC) being held in National Harbor, Maryland.
Today’s post explores the concept of immunocytokines, engineered antibodies that are designed to boost the immune system, so that subsequent therapies will be more effective.
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