Biotech Strategy Blog

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

Posts tagged ‘TIM-3’

Is TIM–3 the next important checkpoint target?

One of the most important challenges in cancer immunotherapy is overcoming immune resistance. For example, even with the high response rates seen in acute lymphoblastic leukemia (ALL) with CAR – T cell therapy, a significant number of patients relapse after an initial response.

Chinatown Honolulu

Chinatown, Honolulu 2016

Could immune resistance be reversed or prevented by the addition of appropriate checkpoint blockade? Which ones matter though, that is the critical question?  Rather than randomly picking ones to try, we need scientific evidence regarding these choices.

This post explores some of the latest data presented at the BMT Tandem meeting on the role of T cell immunoglobulin mucin–3 (TIM–3) and PD–1 upregulation in causing resistance.

If you’re not already a sub and want to read our coverage of ASH, BMT Tandem and the forthcoming AACR 2016 annual meeting, you can purchase individual access below. This week only – inspired by the story of Eddie Aikau in Hawaii – we have a special offer that we’ve never done before (and may never do again) of $75 off a quarterly subscription. The deal ends tomorrow Friday March 4th at 12 noon HST. Check it out!

Subscribers can login to read more about the latest data on how alternative checkpoint inhibitors may have a role to play in cancer treatment.  Welcome to the new folks who signed up this week, good to see y’all!

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Novel Targets Podcast 6 – Immune Agonists

Vienna Torte

Which of these cakes will you choose?

Greetings from Vienna where we are gearing up for our coverage of the European Cancer Congress (Twitter #ECC2015).

We’ll be writing a “highlights” post for subscribers at the end of the day here on Saturday, Sunday and Monday, then will follow- up with more in-depth coverage after we have talked with experts about the data presented.

Checkpoint Inhibitors and Cancer Immunotherapy are not surprisingly hot topics at the meeting.

In case you missed it, this month’s episode of Novel Targets (are we really on show #6 already?!) takes us on a new branch of the journey looking at various aspects of cancer immunotherapy:

Boosting T cell production – Stepping on the Gas

In past shows, we’ve looked at unlocking the brakes (checkpoint inhibitors), immune biomarkers (MDSCs and STING pathway), an inflamed or immunologic tumour type (lung cancer), a non-inflamed tumour type (prostate cancer), adoptive cell therapies and now it’s time for something really different… what happens when we literally step on the gas with immune agonists?

That’s the theme of the latest show – listen to Episode 6 on SoundCloud or iTunes (open access thanks to our sponsors, Genentech).

This article focuses on more detailed background and show notes for BSB subscribers.

It’s an important topic that is both simple in concept to understand and yet highly complex in terms of optimising therapy.

It’s time to take a deeper dive…

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Checkpoint inhibition: targeting TIM-3

Over the last couple of years we have heard much about targeting various checkpoints that exert an inhibitory effect on the immune system and the T cells, in particular.  The main targets where we have a growing body of evidence to date are CTLA-4, PD-1 and PD-L1, but there are others including LAG-3, TIM-3, ICOS etc.

Earlier this year at AACR, we saw new evidence that combining two checkpoints (anti-CTLA4 and anti-PD1) was superior to monotherapy in metastatic melanoma, albeit with a concomitant increase in toxicities.

What about the other inhibitory signals though?  Are they bystanders, much like passenger mutations that have little effect, or do they matter, at least in some tumor types?  If so, which ones?

We took a look at some of the emerging data associated with targeting TIM-3 – the results may well surprise some observers.

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AACR Gems from the Poster Halls in ImmunoOncology

After yesterdays post on Gems from the Poster Halls at the American Association for Cancer Research (AACR) in Philadelphia where we took a look at new developments in targeted therapies, several subscribers asked for a repeat, but with a focus on immuno-oncology.

AACR 2015 Checkpoint Inhibitor PostersThere are a number of elements that many people are interested in, especially given the Merck and BMS clinical data at AACR, where we clearly saw that:

  • Anti-PD–1 therapy with pembrolizumab is superior to anti-CTLA4 with ipilimumab in metastatic melanoma (expect nivolumab to show the same thing at ASCO)
  • Combined PD–1 plus CTLA4 blockade (with nivolumab plus ipilimumab) was superior to anti-CTLA4 alone, but with higher grade 3/4 toxicities, also in advanced melanoma

Sadly though, we still see that 70-80% of patients don’t respond to these therapies.

  • How can we improve on that?
  • What happens when we explore other factors, tumour types and different aspects of the immune system?
  • What can we learn about novel sequencing or combination approaches?
  • Which ones look interesting?

Endless questions can be asked – to which we still have too few answers – although there were some encouraging signs and hints of possibilities at AACR.

The 2015 AACR program was particularly challenging this year with lots of really good symposia and general sessions, making it tough to whizz round the vast poster hall spread out around the exhibits as well.  To give you an idea of scale, it was pretty typical to cover 17K to 18K steps a day, approximately 7 to 8 miles.  For many people, fitting in a quick lunch and the posters was certainly a challenging feat, depending where you were in the complex.  With a morning session ending at 12.30pm, the afternoon session starting at 1pm and 2,000 steps between the Grand and Terrace Ballrooms, you sure had to get your skates on, Beep Beep!

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6 important things I learned from AACR 2014 on immuno-oncology

 

“Nothing lasts forever, because nothing ever has.”

James Shelley, The Caesura Letters

This year’s annual AACR meeting was so good, we could probably write another 50 posts and still not be done! With ASCO fast approaching, however, it’s almost time to draw it to a close and the final post conference note will be published on Monday.

Today is the penultimate report and focuses on the key highlights that caught my attention in immuno-oncology, which covers the gamut from checkpoint inhibitors, co-stimulants, innate immunotherapy and CAR T cell therapy to bispecific antibody TCRs.

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