This is an extended update that I’ve been planning to write for some time, however, there was always some shiny new clinical data to highlight and discuss so it sadly stayed on the backburner!
Is the sun rising on CAR-T cell threats from the East?
Over the next few weeks, we will post some meaty reviews on various topics pertinent to cancer research R&D. They might involve a particular tumour type that is seeing extensive developments, an important or difficult target, or even a particular category approach, for example.
In the first of this new mini-series, we take a look at the CAR-T cell therapy niche and highlight some important new developments that are well worth watching out for.
Things are a-changin’ very rapidly here, including numerous R&D threats from the east (China) so it’s a good opportunity to take stock and look forward.
Here we go – hold on to your hats…
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Now that at two CAR T cell therapies have been approved by the FDA in two indications, what does the future hold for new developments in both hematologic malignancies and solid tumours?
It was astonishing to explore the poster halls at AACR last month and see just how many new players and targets are emerging left, right and centre.
Last week we highlighted an up and coming new player on the scene, Mustang Bio, but what about the original pioneers in this niche and what are they up to these days?
To answer this question, we tracked down Dr Renier Brentjens at Memorial Sloan Kettering while in Chicago to learn more about his latest work and where he sees the future of CAR T cell therapy heading. It makes for a very interesting, and at times, surprising read…
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After extensive – and at times, intensive – preclinical and clinical research on the adaptive immune system and how best to activate the cytolytic T cells in both hematological malignancies and solid tumours, attention is beginning to increase on the innate immune system. In particular, researchers are investigating how approaches in this realm can be incorporated into rational combinations with adaptive therapies, such that outcomes might be improved more than with either alone.
Human NK Cell Source: NIH
There are a number of ways to activate the innate immune system and direct dendritic or NK cells, for example. Some therapeutics seek to boost the responses via different innate sensing pathways such as cGAS/STING or CD47/SIRPα, for example, while others involve targeting stimulatory cytokines, chemokines, toll-like receptors (TLRs), etc through various agonist molecules.
There are also a myriad of vaccination strategies to consider involving neoantigens or neoepitopes, not to forget NK cell infusions, various NK CARs, bi/trispecifics and even checkpoint blockade of NK related targets.
These development have typically not received the same amount of attention as their T cell cousins, but it’s certainly an active and fertile area of research and one that we are likely to hear more about going forward as new developments start to make their mark.
In a world of ‘T cell chauvinists’ – to quote Dr Adi Diab (MD Anderson) – let’s not forget or ignore the humble NK cells, which also have cancer killing abilities.
Over the next three weeks, we have an extended mini-series focusing on NK cells rolling out with interviews and commentary from academia and biotechs alike across both sides of the pond. It promises to be an interesting and provocative ride with plenty of critical questions to pose and resolve along the journey.
So, hang onto your hats for the first part of the journey…
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How Will Adoptive Cell Therapy Crack Solid Tumours? – This was the provocative question raised by the title of Dr Malcolm Brenner’s keynote lecture at the 2018 ASCO-SITC Clinical Immuno-Oncology Symposium held last week in San Francisco, ”Adoptive T cell Therapy: Target Solid Tumors by CARs or TCRs?”
Malcolm K Brenner, MD PhD is the Director of the Center for Cell and Gene Therapy at Baylor College of Medicine in Houston, Texas.
ASCO have just named CAR-T cell immunotherapy as its “2018 Cancer Advance of the Year” so it’s timely to take a look at where we are in the adoptive cell therapy field and where it may be going?
We’ve been writing about adoptive cell therapies (ACT) such as CAR T cell therapy since 2011. Indeed, I vividly recall one of my early interviews about it at ASH 2013 (See post: Juno Therapeutics takes on Novartis and seeks to revolutionize the treatment of blood cancers – an interview with Renier Brentjens)”.
In recent years, CAR T cell therapy has made tremendous progress in hematologic malignancies, gaining FDA approval last year in relapsed/refratory paediatric ALL and non-Hodgkin lymphoma (NHL). We have not seen the same efficacy in solid tumours as yet, and this remains one of the key challenges in the field today.
In this post, we take a look at the perspectives Dr Brenner offered in his keynote lecture at ASCO-SITC and the potential impact they may have on the landscape.
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Sunset in Puerta del Sol, Madrid
This is the last of our conference previews for #ESMO17 – after this we move on to the emerging data coming out from Madrid.
Most of the attention is rightly focused on the big phase 3 trial readouts that are eagerly expected, but what about some of the hidden gems from smaller companies?
What new IO and immunotherapies are looking interesting this year?
We have five such highlights for readers to watch out for. Things should get quite interesting over the next week or so.
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Part 3 of our series on Gems from the Poster Halls at ESMO continues with a look at another four important combination studies that may be of keen interest to readers.
These include both targeted therapies as well as immunotherapies.
Some of the posters I was originally keen to write about turned out a little unexpectedly with some issues to address i.e. lack of efficacy or unwanted toxicities based on the dosing schedule used and may require tweaking of the dosing, schedule or trial design. Others will unfortunately be destined for dog drug heaven unless a new tumour type offers more promise. Such is the R&D roller coaster that is oncology – sometimes we forget that more compounds fail than make it market.
The good news is that there were plenty of promising approaches that are worthy of writing up and discussing. In the third part of our poster mini-series, we take another deeper dive with a careful look at some new data in Copenhagen.
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What questions are BSB readers sending in to us this month?
I wanted to take a moment out of AACR Previews and catch up on some recent news that is intriguing or perplexing subscribers. All questions are anonymous and in many cases, the same questions were actually sent in by multiple people, a testament to what’s top of mind in oncology lately.
Today, we cover a Q&A on a variety of topics on Kite Pharma (the Genentech collaboration and their TCR in solid tumours), a discussion about EGVRvIII in glioblastoma, and Gilead’s woes with idelalisib and an IO pipeline.
So let’s get started – subscribers can sign-in…
The immuno-oncology space continues to get both interesting and also very crowded with over 20 chimeric antigen receptor (CAR) T cell therapies now in development. Originally, the excitement began with the University of Pennsylvania’s dramatic announcement regarding the first two advanced CLL patients they successfully treated, leading to a collaboration with Novartis and spurring a new ‘arms race’ development in this niche.
While most of the CAR T cell therapy data since has largely focused on acute lymphoblastic leukemia (ALL) and to a lesser extent, non-Hodgkins lymphoma (NHL), many have been wondering what was happening on the CLL front? Has hope been abandoned there or will we see a renaissance occur? It is of particular relevance with the Abbvie/Genentech announcement that venetoclax has positive data in CLL patients who have the Del17p mutation and filing is likely here in this subset soon. Therapies such as ibrutinib and idelalisib are already approved in refractory CLL and may also have a future role to play here.
Do we need suicide switches for CAR T cell therapies such as Bellicum and Cellectis are developing or not?
Meanwhile, other hematologic malignancies are also being explored, including multiple myeloma. Why would a CD19 CAR work in a disease long considered to be CD19-negative in advanced, refractory disease?
Dr Carl June, U Penn
What about progress with solid tumours? Many commentators and investors have been highly sceptical of the chances of success here following the advent of positive checkpoint data beyond metastatic melanoma and early CAR data in mesothelin cancers.
To answer these questions and also get a flavour for where things are headed with CAR T cell therapies, we recently interviewed one of the leading experts in this field, Dr Carl June (U Penn).
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