Biotech Strategy Blog

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

Posts tagged ‘immunotherapy’

Aloha! It will soon be time to pack your Hawaiian shirts for the forthcoming BMT Tandem Meeting in Hawaii (Twitter #BMTTandem16 – what a long hashtag!!)

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Commonly known as “Tandem,” it’s the combined annual meetings of the Center for International Blood & Marrow Transplant Research (CIBMTR) and the American Society for Blood and Marrow Transplantation (ASBMT).

Hawaii is great location for a meeting in February, and one that I’m sure will generate a lot of envy for those who can’t attend and are stuck in the winter cold and chill. Who said we don’t go the “extra mile” for BSB subs?

One of the presentations I’m looking forward to hearing at Tandem is by Ann Leen, PhD, who is an Associate Professor at Baylor College of Medicine.

Dr Leen will be talking about “Immunotherapy for Lymphoma using T cells Targeting Multiple Tumor-Associated Antigens.

At last December’s ASH annual meeting, Dr Leen presented preliminary data with this novel approach in patients with Hodgkin’s Lymphoma (HL) and non-Hodgkin’s lymphoma (NHL). After her ASH presentation, she kindly spoke to BSB.

This post is part of our post-meeting ASH15 coverage, and our ongoing coverage of some of the exciting developments in immuno-oncology.  In case you missed it, do check out the ASH interview with Seattle Genetics CEO Clay Siegall, PhD.

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Beyond the late breaking abstracts and plenary sessions at the European Cancer Conference being held in Vienna, Austria later this month, what other important topics can we expect to hear about?

ECCO 2015 Vienna

We covered the former in the last article on Biotech Strategy Blog, today we turn our attention to the proffered (oral) sessions and what we can learn from those sessions and the expected data that is due to be presented.

There are a number of interesting topics and new data slated for presentation that are worthy of review and highlighting in a What To Watch out For (W2W4) format.

Here’s our take on the potential highlights at the meeting.

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At the recent American Association of Immunology (AAI) and American Society of Gene & Cell Therapy (ASGCT) meetings in New Orleans, we had the good fortune to interview a number of leading cancer immunologists about their work. Some of these have already been published either here on Biotech Strategy Blog, or on the Novel Targets podcast.

In the meantime, the huge tsunami of data from the annual meeting of the American Society of Clinical Oncology (ASCO) hit and we have been a bit backlogged! Time to address that and focus on some more thoughtful reflections about where the cancer immunotherapy field is going.

Already, we are seeing another round of new collaborations and deals hit the newswires with AstraZeneca announcing two collaborations, one with Inovio on the INO–3112 HPV cancer vaccine and another with Heptares, where they acquired the exclusive global rights to develop, manufacture and commercialise the adenosine A2A receptor antagonist, HTL–1071. The first involves a cancer vaccine and the second immune escape mechanisms.  Not to be outdone, their rivals Clovis also announced a collaboration with Genentech to explore rociletinib (EGFR T790M) with atezoliumab (anti-PD-L1) in EGFR mutation-positive lung cancer.

Cancer vaccines have not, however, been a very successful or fertile area of R&D for Pharmaland to date, with only one such therapy approved by the FDA (sipuleucel-T or Provenge) and literally hundreds of other such compounds consigned to dog drug heaven. This illustrates the sheer enormity of the task we need to undertake in stimulating the body’s immune system to successfully attack the cancer in a sustained and robust way.

Dr Rosenberg, NCI

Dr Rosenberg, NCI

Despite this setback, there is still notable interest in exploring the innate immune system and finding effective ways to target and stimulate the T cells or T lymphocytes to attack the cancer.

One man who has accomplished an incredible body of work over the last two to three decades is Dr Steven Rosenberg from the NCI’s Surgery Branch (right).

No one who attended any of the cancer conferences where he spoke at over the last year is ever going to forget the dramatic before and after slides of remarkable transformation in his patient case history examples using Tumour Infiltrating Lymphocytes (TILs) as this example illustrates:

 

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One of my favourite meetings of the year in our conference calendar is the American Association for Cancer Research (AACR) annual meeting, which is held in the spring. In years past, the agenda at this event has set the scene for the rest of the year in terms of emerging new trends, particularly with regards to targeted therapies. In the last two years though, this hasn’t been the case, as adjusting to the brave new world of immunotherapies has taken some time.

The good news is that AACR has come roaring back in 2015 with a star-studded line-up that includes some of the big hitters and sluggers in the cancer immunology space.

What’s in store for this year, you may well be wondering, and where are we likely to see the new trends evolve?

We took an in-depth look at what’s hot in immunotherapies and where the new directions are going in this latest conference preview, the first one in series relating to the AACR annual meeting being held in Philadelphia from April 18–22nd (Twitter #AACR15).

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One of my favourite sessions at any cancer conference is the science symposia, although they go under many different guises and names. At the European Society of Medical Oncology (ESMO) they are known as Special Symposia and conceptually are very similar to Clinical Science Symposia at ASCO.

ESMO 2014Here at these sessions, top thought leaders in the space debate and lecture on key issues of the day. They’re usually packed with information and are well worth attending, even in a hectic schedule.

Interestingly, immuno-oncology has a dominant focus on the program for the first time since I’ve been attending ECCO/ESMO events over the last dozen years or so, demonstrating how quickly it is being assimilated into the scientific and clinical consciousness.  Years ago, I attended a session on autologous cell therapies (ACT) and there were maybe a handful of us in the room.  In Madrid, I doubt if there will be 12 empty seats in the theatre and it will probably be what Pharmaland calls SRO – standing room only.

So what can we learn from the announced sessions this year?

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Today, I’m going to summarise some of my notes on what we learned about lung cancer and immunotherapy at AACR. The burgeoning immuno-oncology topic is way too big to do justice in one single post, so over the next couple of days, you’ll find a mini series evolving here on BSB to cover many of the points relating to checkpoint inhibitors from AACR. It was the first time in 15 years I’ve seen immunotherapy dominate a basic scientific meeting and it was good to see it happen. It is definitely very much the focus – and excitement – of many major cancer centres in the US.

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“You may say I’m a dreamer

But I’m not the only one.”

John Lennon, Imagine

As part of our ongoing series on the AACR Previews, today I want to take a closer look at some interesting scientific and clinical data in triple negative breast cancer (TNBC).  One reason for this is that we need to remember that the disease, as currently defined, is essentially what’s left after taking out the ER+, HER2+ and inflammatory breast cancer subsets. In other words, it’s a very heterogeneous catch-all population, making clinical trials rather challenging at best. It also means that the chances of success in general all-comer trials is rather low.

It is my hope that as we learn more about the biology of this disease, we may see further subsets be defined by molecular peculiarities, much in the same way that gastrointestinal stromal tumours (GIST) were defined by KIT expression and CD117. Once we have more homogenous subsets, it will be easier to conduct trials just looking at those specific patients, thereby improving the chances of clinical success with therapeutic intervention.

There’s been a lot of work focused on this area over the last few years, so it seems a good point to find out where the progress has got to.

Without much further ado, what can we learn about the biology of TNBC from AACR this year and which potential new targets might emerge?

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Beyond the noise of the exciting the data in CAR-T cells, CLL, NHL and multiple myeloma, one of my favourite pastimes at cancer conferences is to look out for up-and-coming gems in the poster halls.

By this I mean interesting novel targets or very active agents in the pipeline.

One of the most eagerly awaited targets on my list was the Killer Immunoglobulin-like Receptor (KIR). It may be a key part of overcoming lymphoma resistance and inducing cell death. If you don’t kill the cancer cells, you likely won’t see remissions occurring.

Companies mentioned: Innate Pharma, BMS, Roche
Products mentioned: IPH2101, IPH2102 (lirilumab), ipilimumab, rituximab, obinutuzumab, anti-PD-1, anti-PD-L1

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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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Background

For many years, scientists have tried – and failed – to develop techniques to activate the body’s immune system against cancer. The majority of these immunotherapy approaches, especially vaccines, simply didn’t have enough potency, or were based on a weak target that had little impact on advanced disease. The rationale for vaccines in cancer prevention is much stronger, as we have seen with the HPV vaccines, Gardasil and Cervarix, for example. When given to patients with advanced disease, the large tumour burden is usually too much for them to overcome and the cancer wins.

Although the immunotherapy field in oncology has been largely a graveyard with millions of dollars wasted and lost, there have been some notable successes. US approvals include rituximab (and other similar CD20 targeted antibodies) in B-cell malignancies, the IMiDs (thalidomide, lenalidomide, pomalidomide) in multiple myeloma, and ipilimumab, a human cytotoxic T-lymphocyte antigen 4 (CTLA4) antibody in metastatic melanoma.

There are several interesting challenges with immunotherapies that must be overcome before successful therapeutics can be developed.

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