Biotech Strategy Blog

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

Posts tagged ‘T cells’

Preview of CICON18 – Part 2

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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Jumpstarting the immune system with synthetic immunity

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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SITC 2016 Can Nektar Boost Checkpoint Performance

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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What are neoantigens and why do they matter in cancer immunotherapy?

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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New developments in allogeneic cellular therapies

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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Immunoscore validated as an important biomarker for colon cancer

We’ve been following the work of Dr Jérôme Galon, a French immunologist, on Immunoscore for a while now, and many readers will remember the last interview he kindly gave BSB from the European Cancer Conference in September [Link].

IMG_6454In 2015 the large global trial to validate Immunoscore as a biomarker was still ongoing, so if you want some background to this important concept, do check out Dr Galon’s interview as it’s well worth reading as a primer on immunosurveillance, the importance of immune cells – the type, density and location, as well as background on the Immunoscore test as a marker of outcome.

Since then, the group have also published some related data that both moves the field forward and offers a way to unify some important concepts in colorectal cancer.

In Chicago, the really good news was that the final results of a large global study involving nearly 4,000 patients were presented to a packed audience in the main hall where the plenary is held. It’s not often you see the gastrointestinal oral session allocated the prime time room over lung or breast cancers – the atmosphere was certainly electric with anticipation!

This week’s post ASCO mini series focuses on colorectal cancer, with a look at several important aspects of this disease as we learn more about the underlying biology, as well as how the immune system functions and how we can use that scientific knowledge to improve outcomes for patients, sometimes in a dramatic way.

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Mixed results with Macrogenics enoblituzumab at SITC

SITC Day 4 Highlights

It’s been an interesting annual meeting at the Society for Immunotherapy of Cancer (SITC) so far and not without controversy either, as the reaction to Incyte’s IDO1 data demonstrated on Friday when combined with Merck’s pembrolizumab (sse post).

Today, we heard the results from another early trial with a novel immune target. This time it was the turn of Macrogenics, a local biotech based up the road in Rockville, Maryland.

They are developing a number of monoclonal antibodies to a variety of targets, including B7-H3. After the controversial late breaker session on Friday, how did their drug fare in the hotseat here in National Harbor this morning?

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Is ocrelizumab a game changer in MS?

At the 2015 European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) meeting Barcelona on Friday, Dr Stephen Hauser (UCSF) presented the data for octrelizumab, an anti-CD20 monoclonal antibody, on behalf of the investigators in the OPERA trial.  This study compared octrelizumab to a standard of care at the time the study started i.e. IFN β-1a (Rebif).

Roche previously announced that ocrelizumab is the first investigational medicine to show positive pivotal study results in both relapsing and primary progressive forms of multiple sclerosis (MS):

  • Ocrelizumab showed superiority to interferon beta-1a (Rebif®) in two identical Phase III studies in people with relapsing multiple sclerosis (MS), the most common form of the disease.
  • Ocrelizumab is the first investigational medicine to show efficacy in people with primary progressive MS in a large Phase III study.

In addition, Dr Montalban presented the latest data for octrelizumab in primary progressive MS versus placebo (there are no approved therapies for this segment) on behalf of the ORATORIO investigators.

Here on BSB we have extensively covered other anti-CD20 monoclonal antibodies such as rituximab, ofatumumab and obinutuzumab in oncology indications specifically associated with hematologic malignancies, so what’s special about this same target and the results in MS with a different chemical entity?

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Update on anti-PD-L1 cancer immunotherapy

In the second part of our mini-series on immuno-oncology, I thought it would be a nice idea to share a recent interview conducted with one of Roche/Genentech’s leading researchers in this field.  I was particularly interested in their approach because while BMS and Merck have clearly focused on anti-PD-1, Roche and Genentech have effectively zigged with their development of an anti-PD-L1 inhibitor.  Does this matter?

Here, we explore the general background to this approach and, in particular, where the company are going with their anti-PD-L1 inhibitor, MPDL3280A.

Topics discussed:

anti-PD-L1, anti-PD-1, anti-CTLA-4, checkpoint point inhibitors, T cells, biomarkers.

Drugs mentioned:

MPDL3280A, nivolumab, MK-3475, ipilimumab (Yervoy), lirilumab, BMS-986016 (anti-LAG3), bevacizumab (Avastin), erlotinib (Tarceva), vemurafenib (Zelboraf), cobimetinib.

If you are interested in more background on how the PD-1 and PD-L1 inhibitors work, you can check out the mechanism of action (MOA) in our video preview from ASCO last year, which explains this in fairly simple terms.

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The future of cancer research – what I learned from the AACR Targets meeting Part 1

As cancer becomes increasing complex with adaptive responses to therapeutic intervention, so our knowledge and strategies for overcoming it must also adapt and improve. Immunotherapy – in several forms – is probably the hottest topic on the landscape at the moment with both checkpoint inhibitors and chimeric antigen receptor technology (CART) vying for air time and attention but where are these approaches going and how can we harness the immune system more effectively?

One of the things I like most about AACR meetings is that there are nearly always some strategic gems emerging from the scientist-physician thought leaders if only you stop to think about how the field can rapidly change by looking at the early patterns that are emerging.

Here’s the first part of a synopsis of what I learned at the recent Molecular Targets meeting in Boston, some of these findings may well have a major impact on cancer research over the next few years…

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