Biotech Strategy Blog

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

Posts tagged ‘T cells’

A high tide marker stands out on the beach, what stood out at ASGCT20 for you?

As Covid–19 continues to exert its impact on the cancer conference schedule, the good news is that it isn’t a total wrecking ball effect as organisations turn to virtual meetings to enable researchers to share their work.

Some of the events we have ‘attended’ this year have been prerecorded in advance, while others have taken the form of live events. Having listened to both, I can say they have advantages and disadvantages either way.

To me, it doesn’t really matter if you are flexible and appreciate the effort the scientists are making to show their wares.

This week it’s the turn of the American Society of Gene and Cell Therapy (ASGCT) to be in the spotlight with a truly ‘live’ meeting.

In the latest post, we focus on some key Gems from the Poster Halls…

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In the fourth part of our mini-series in novel targets and agents in development we turn to novel cell therapy approaches that are perhaps under the radar for many observers.

While these might seem bleak times during a pandemic, there’s always a silver lining somewhere

While much attention has been focused on antigen loss or downregulation of the target wih adoptive cell therapies, research continues to evaluate various solutions to the problem.

One obvious way is to develop dual CARs or target multiple antigen targets of relevance to the tumour type being investigated.

There are other potential solutions being looked at, both in preclinical animal models and in translational work using cells from people treated with HSCT or CAR T cell therapies.

Here, we look at an alternative immunotherapy approach, which with time may have utility in both hematologic malignancies, as well as solid tumours…

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Whipping up the CAR-T cell niche

In the sixth and final part of the latest CAR-T cell therapy mini-series, we take a look at a really key factor that will need to be addressed if we want to move forward in both hematologic and solid tumours in terms of improved outcomes.

To be clear, this is not about the obvious – tackling immune suppression – but something entirely different!

Now, that might well mean incorporating new regimens in the process or it could lead to version 3.0 in terms of new constructs to be tested in the clinic in due course.

What’s not to like?

Added bonus in this review is that it’s not one voice expressed here, but rather the consolidated perspective of four different experts, so you can quickly see clarity and differences of opinion on several topics…

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In our latest expert interview, we depart from the usual focus on one of two particular or narrow topics and indulge in a more wide ranging discussion to explore a variety of issues facing the IO field and look at them from the perspective of a researcher who is experienced in working with antibodies in various forms.

We cover a lot of ground from CAR-T cells to bispecifics to NK cells – while many people in industry may see these approaches as separate modalities in different niches, in the future we may well see a greater convergent and opportunities for regimens and combinations rather than a more nihilistic either/or approach.

I have long been fascinated with design of molecules and how different tweaks or enhancements can change the way something works – for better or worse. Just as we have learned much from immune agonists and their biphasic curves that result from constant stimulation (and ways to fix that too), so too will we see CARs, T cell engagers, and NK cell therapies adapt and improve in terms of how they are constructed.

Who better to talk about these changes and the learnings to be had lately than someone who has built and tested many antibodies for a living and is now running his own company?

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For today’s post, we’ve curated our individual highlights from the tsunami of data that flew thick and fast yesterday between science sessions, oral presentations and poster hall gems.

There were some pleasant surprises in the mix, to be sure, plus the weather brightened up immeasurably!

Yesterday’s lunch time ASH Dash was quieter than usual

Having whittled the number of trial highlights for review and critique down to thirteen key insights and learnings, what made our joint list?

To find out more, check out the post below!

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Increasingly we are seeing more research on the inflammatory status of the tumour microenvironment (TME) in recent years, not to mention the impact of cytokine and chemokine signalling pathways, and how they can be manipulated therapeutically.

There’s also a much wider range of novel immunotherapy approaches being evaluated such as checkpoints, CARs and vaccines with respect to both T and NK cell therapies. There are also a few other immune cells being targeted for developmental therapeutics.

As part of the ongoing CICON18 Preview series, we take a look at what’s in store and why the latest ten we’ve highlighted matter in the broader context of the evolving landscape…

For those who missed it, Part 1 can be found here.

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Here we are with Part 2 of our latest mini-series on novel ways to jumpstart the immune system so that subsequent therapy can be more effective, leading to improved outcomes.

In Part 1, we looked at the preclinical and scientific evidence regarding a novel approach to modulate a cold or non-inflamed tumour type, thereby turning the phenotype into a hotter or inflamed one.

In principle, this concept sounds quite simple in theory, but in practice it’s actually much more technically challenging to do than many realise, especially when we consider not just the design of the antibody itself and perhaps even efficacy, but also the convenience of administration and tolerability, both as monotherapy and also in combination with other therapies.

What’s up on deck today is not one, but three interviews, offering readers a candid look through the keyhole at varied insights from different perspectives around a central R&D topic, namely…

What do you do when you have a new compound in clinical development and wish to explore how to integrate it – do you use it with an existing framework or try something new and different? What about other compounds that might be competing with it internally?

It’s a question every single oncology company faces when a new molecule moves out of preclinical development into phase 1 trials. What next?

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National Harbor Maryland

National Harbor, MD

The range of different types of cancer immunotherapies in the clinic now is fairly broad, with many promising approaches being evaluated.

Cytokines, despite their initial challenges with toxicities, are an essential pillar of this approach, along with checkpoint inhibitors and agonists, adoptive T cell therapy, and now even neoantigen approaches and cancer vaccines.

Nektar Therapeutics ($NKTR) are developing two intriguing immuno-oncology compounds based on cytokines, which are in early development called NKTR–214 and NKTR-255.

The idea behind this approach is that they are immuno-stimulatory therapies designed to expand T cells and Natural Killer (NK) cells directly in the tumour microenvironment, thereby increasing expression of PD-1 on these immune cells.  Subsequent checkpoint therapy could potentially be made more effective. We already know that those patients with few or no T cells are less likely to respond (cold or non-inflamed tumours) so the hunt is on finding ways to address this particular challenge.  Can it be done therapeutically?

Data was presented this past weekend at the Society for Immunotherapy of Cancer (SITC).

Was the data encouraging enough to justify further clinical development or is this a compound headed to dog drug heaven?

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Great Fire MonumentThe Great Fire of London started 350 years ago in September 1666 following a fire in a Pudding Lane bakery.  It highlights the potential of what a small fire can do once it takes hold – over the course of 3 days, 13,000 houses and 436 acres were destroyed.  It forever changed the landscape of medieval London.

The Monument (pictured right) to commemorate the Great Fire was designed by Sir Christopher Wren. Constructed from 1671 – 1677, it is 202 feet in height, the distance to the bakery where the fire started. You can even walk up it, if you are in the area.

When we think about cancer immunotherapy, one of the emerging important trends is the need to “inflame” or set fire to the immune system, especially in those cancer patients who don’t have a pre-existing immune response.

We want to ignite the immune system, in the hope that it will create the equivalent of the Great Fire…

Great Fire of London Plaque

In this post we’re starting at mini-series looking at neoantigens, beginning with a primer on what they are and why they matter in cancer immunotherapy.  In subsequent posts we’ll look at some of the innovative ways companies are identifying and targeting them.

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HMS VictoryThe dog days of summer are usually quiet on the Pharmaland front, although this year has been a bit of an exception, being notable for a batch of deals being completed and announced already.

The cell therapy space is one area that has courted both controversy and new collaborations, for example. Nary a week seems to pass without something appearing in the news! This has proven pretty interesting for a number of subscribers, who write in asking plenty of astute questions.

Today’s questions from BSB readers therefore encompass allogeneic cell therapies and what’s going on in that fast moving dynamic space.  Not all of the announcements may be what they seem though, and some are much more riskier than others.

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