Biotech Strategy Blog

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

Posts tagged ‘innate immunotherapy’

Over the last year or two, we have covered a number of different pathways that are involved with the immune system including CD19 and 20, CTLA–4, PD–1 and PD-L1, IDO1, CD40, OX40, TIGIT, ICOS and others.

Today, it’s the turn of an oncoprotein called NY-ESO–1 that has been garnering quite a bit of attention of late and will also be highly relevant to some upcoming posts and thought leader interviews we have scheduled here on Biotech Strategy Blog. It’s always a good idea to cover the basics first, before exploring the more advanced concepts.

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Marcel R.M. van den Brink, M.D., Ph.D.At the 2014 Society for Immunotherapy of Cancer (SITC) annual meeting at National Harbor, MD, one of the presentations that caught my attention was by Marcel van den Brink MD PhD (@DrMvandenBrink), pictured right, from Memorial Sloan-Kettering Cancer Center in New York. (picture courtesy of MSKCC with permission).

Dr van den Brink, who is Head of the Division of Hematologic Oncology and Alan.N. Houghton Chair, gave a fascinating talk entitled, “The role of the Intestinal Microbiome on GvHD” (Graft versus Host Disease).

Think of the yogurt pots and probiotic drinks we see in the supermarket with “beneficial” bacteria. We’re familiar with the idea that the make up of the millions of bacteria in our gut can make a difference to our digestion and health.

Well, it turns out it can make a difference to our immune system too. Research presented at the recent SITC meeting by Dr van den Brink showed that manipulating the bacteria in the gut could potentially help the thousands of patients around the world who receive a bone marrow transplant (BMT).  BMT is a gruelling procedure that many leukemia, myeloma and lymphoma patients have to face as part of their treatment protocol.

Sadly, about 20%* of people who receive an allogeneic bone marrow transplant from an unmatched donor die from Graft versus host disease (GvHD)

* According to 2010-2011 data from the Center for International Blood and Marrow Transport (CIBMTR), GvHD was the cause of death in 19-23% of people who received an allogeneic hematopoietic stem cell transplant.

After his informative and interesting presentation at SITC, Dr van den Brink spoke with BSB about his findings and what’s on the horizon for the treatment of GvHD.

Over the course of a half hour conversation, he covered some of the new treatment options, one of which may change the standard of care, and the rational some companies are pursuing by targeting the innate immune system.

For those interested in CAR-T cell therapy and the promise of allogeneic CAR-T cells, Dr van den Brink kindly talked about some unpublished data from MSKCC about why we have not seen GvHD in patients who receive allogeneic CAR-T cells.

GvHD is an important topic, and one that deserves more attention. I expect we will here a lot more about it at ASH this year so reading this interview will, hopefully, help you better put that data in context.

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Immuno-oncology is one of the hottest topics, if not, the hottest in cancer drug development at the moment, and every conference seems to advance the field forward. The pace of progress is breathtaking as thought leaders and pharma & biotech seek to maximize how to leverage the body’s immune system in the fight against cancer. It’s exciting times!

Coming up next on the calendar are two cancer conferences, the Society for Immunotherapy of Cancer (SITC) held in Maryland later this week, followed swiftly by the EORTC-AACR-NCI Molecular Targets conference (often referred to as the Triple meeting by industry insiders) in Barcelona just before Thanksgiving.

SITC 2014 Immunotherapy Banner

Whoa, that’s a lot of data yet to come, and then in December we have the American Society of Hematology (ASH) and San Antonio Breast Cancer Symposium (SABCS).

Back home in the Blighty, November is often referred to as the ‘month of the drowned dog’ because it rains a lot… at this rate it’s more like raining data – let’s hope not too many agents are headed for dog drug heaven! The good news for subscribers is there’s a lot of conference coverage to come!

2014 ESMO Congress Poster HallSo here we are, after nearly two dozen posts, it’s time to close out the 2014 ESMO coverage with a final review of the immuno-oncology posters that piqued our interest.

There were 16 in all that fitted that category. Normally, we highlight three or four gems from the poster halls, so more than a baker’s dozen is quite a feast.

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Melanoma oral abstracts at ASCO 2014The melanoma oral abstracts session at ASCO 2014 was packed as a full house in the Arie Crown lecture theatre listened to the latest on new immuno-oncology therapies that are leading a revolution in melanoma treatment.

In the Clinical Science Symposium on PD-1 blockade and in the oral session at ASCO 2013 we heard how PD-1 antibodies nivolumab, MK-3475 (now pembrolizumab) and the PD-L1 antibody MPDL3280A had high response rates, long durations of response with favourable toxicity. This led to melanoma suddenly becoming one of the hottest areas of cancer drug development.

Global incidence of stage III melanoma continues to rise, with a high 5 year relapse rate (89% in stage IIIc), so there remains a need for more effective treatment options. It’s particularly sad to see so many young people end up with metastatic melanoma from over-exposure to tanning beds or too much sun! After going to several melanoma sessions, I don’t go out as much in the mid-day sun here in Florida.

So what did latest data show at ASCO 2014? Is pembrolizumab better than nivolumab? Will combinations be more effective than single agent therapies alone and will toxicities impact the risk:benefit profile?

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In the past, I’ve sometimes been accused of being a bit of an immunotherapy bear for my dislike of cancer vaccines as a single agent therapy in advanced disease where the tumour burden is very high. That particular field has undoubtedly been a huge graveyard for many companies, much in the same way that metastatic melanoma was, until novel therapeutics and immunotherapeutics emerged to push through the envelope.

To be clear, I am though, a big fan of targeted immunotherapies such as checkpoint inhibitors and chimeric antigen receptor (CAR) T cell therapies, which have been very much to the forefront in immuno-oncology over the last two years and rightly so, with some initial trials showing some very promising results.

Both of those approaches are squarely part of the adaptive immune system and seek, in different ways, to retrain the bodies immune system to fight the tumour. More recently, the innate immune system has seen new advances as reearchers moved beyond simple vaccines to develop more thoughtful and innovative approaches that seek to outwit the very masking the cancer is trying to fool the immune system with. It’s no less exciting, just a different way of looking at the science and improving out understanding of the biology of the many diseases that cancer makes up.

In this AACR preview, I take a broad look at some innovative and novel scientific approaches, including targeting anti-CD47 and SIRPα (Stanford and Stem Cell Therapeutics), KIR and MICA (Innate Pharma) and neutrophils (Biothera).

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This week the Cancer Conference Coverage moves to the joint IASLC-AACR symposium on the Molecular Origins of Lung Cancer in San Diego.  Having attended previous events (this is the third one they’ve hosted) and rather enjoyed them, this year I’m following it remotely.

What’s particularly nice about this type of specialist event is that they are especially useful for chatting informally with attendees and being able to ask a lot of questions that simply wouldn’t be feasible at larger meetings due to time and other constraints.

This review covers my thoughts on two immunotherapies, namely Merck’s anti-PD-1, which was previously presented at the World Lung Conference, plus a completely novel and very different approach that looks really quite exciting.

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