Biotech Strategy Blog

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

Posts tagged ‘tumor infiltrating lymphocytes’

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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Photo: National Institutes of Health

After last week’s post on therapeutic tumor infiltrating lymphocytes (TILs), we received a bunch of questions from readers.

I don’t have time to answer them all in detail individually (sorry!), but it does provide an opportunity to review the evolving landscape and address some of them within the latest article.

It seems to be a good time to take a broader look at T cell manipulation, especially as it pertains to the application of TILs, chimeric antigen receptors (CAR), and T cell receptors (TCR).

We’ve certainly come along way since the historic lecture in 1991 pictured right (photo: National Institutes of Health), but there’s still some way to go before the full potential of cancer immunotherapy is reached.

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Over the last two years we’ve written extensively about chimeric antigen receptor (CAR) T cell therapies, checkpoint inhibitors and immune agonists (stimulants), yet these aren’t the only novel immunotherapies that are being developed to target cancer cells.

One area that hasn’t received a lot of attention is adoptive cell transfer (ACT) and therapeutic tumour infiltrating lymphocytes (TILs).

  • What exactly are these approaches and what progress has taken place so far?
  • Where is this field going in the near future?

Rosenberg ASH14 TIL PresentationTo answer these questions, we put together a primer based on the groundbreaking research of Dr Steven Rosenberg (NCI Surgical Branch), and his invited talk at the recent American Society of Hematology (ASH) meeting.

As Rosenberg himself noted, what they’re doing is pretty daunting and yet, results so far have shown some impressive responses in some patients, especially those with metastatic melanoma, but other cancers have also responded well to this novel approach.

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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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