Biotech Strategy Blog

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

Posts tagged ‘immune escape’

Can this novel combination overcome resistance to checkpoint blockade?

As we demonstrated in the recent Novel Targets podcast that opened Season 3, one topic that is a key focus for many in the IO space is addressing mechanisms of immune escape and acquired resistance to single agent treatment with immunotherapy.

We’ve seen several oncogenic escape mechanisms reported, included activation of the JAK/STAT pathways in some patients and loss of existing immunity when the tumour suddenly becomes cold or an immune dessert.

The good news is that there are a number of ideas that can be pursued, including activating the innate immune system in various combinations.

As we see more companies invest in the innate immunity space in order to have a rational partner with which to combine with their checkpoint inhibitor, it will be important to maintain focus on trial designs and synergistic mechanism of actions to improve efficacy while reducing the potential for overlapping or severe toxicities.

Here’s one intriguing and promising new approach that caught our eye this month that is worthy of researching and following over time…

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Overcoming Cancer Immunotherapy Resistance

The majority of patients do not respond to cancer immunotherapy. That’s a fact. If you don’t have an immune response to start with, there’s no point giving a checkpoint inhibitor on its own because there are no T cells present in the tumor.

Dr Bernie Fox (@BernardAFox), a world leading cancer immunotherapy expert from Earle Chiles Research Institute in Portland, nailed this a year ago on the Novel Targets Podcast:

“What I teach the first year medical students is that if you have metastatic cancer, the only thing that makes a difference in your life is whether you’ve got your immune system turned on. If it’s not turned on, it doesn’t make a difference what you get, chemo, radiation, surgery, you aren’t going to do well.”

Lincoln Memorial, Washington DC

As we have seen with targeted therapies, drugs can also stop working as a result of acquired resistance. This is also true with cancer immunotherapy treatment.  Cancer constantly evolves and finds ways to bypass or evade detection or ways to kill it.

Faced with a complex jigsaw where we only have some of the pieces in place and an evil double sided version as a model for sneaky advanced cancers, where are we in overcoming cancer immunotherapy resistance?

At the recent AACR annual meeting we spoke with a rising star – an up and coming thought leader in the field of cancer immunotherapy who has taken all the disparate information out there and come up with a perspective on where the field is at and where it needs to go.

Jason Luke MD FACP (@jasonlukemd) is an Assistant Professor at the University of Chicago where, as a medical oncologist, he leads multiple early stage cancer immunotherapy drug development trials and treats patients with melanoma.

Dr Jason Luke AACR17

Working with colleagues such as Dr Tom Gajewski, he has a unique perspective on cancer immunotherapy resistance, and how to overcome this. Dr Luke kindly spoke to BSB in Washington DC.

This is the 3rd post in our series of expert interviews from AACR17.

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AACR 2017 Preview 1

In the first of our 2017 AACR annual meeting previews, we are taking a look at a particular theme that we expect to hear much more about over the coming months.

Washington DC cherry blossoms

In order to make something better than what it is, we first need to step back and understand the various factors that underpin it. To do otherwise is akin to the proverbial throwing of mud at the wall and hoping something sticks.

Trying things out just because they seem like a good idea or that’s all you have in your pipeline doesn’t really inspire the greatest of confidence in a clinical trial’s success.

This is also where several factors including tumour biology, cancer genomics, biomarkers, and acquired resistance can intersect to produce some intriguing results.

Please note that our Conference Preview series are never random.  When looking at the abstracts as a whole, we try to organise them around a particular scientific theme or a tumour type. The idea here is that it makes it much easier for our readers to see and grasp emerging concepts and trends. It’s also a deeper dive into the whys; things happen for a reason – why is that?  What can we learn from the process?

These are also not random selections from say, publicly traded or private companies, big or small caps.

It does take more time to roll thematic articles out, but the advantage is that over the course of the next two weeks readers will be better equipped to get a grip on the meeting ahead of the event.

Indeed, a couple of subscribers even told us last year they learned more from our in-depth previews than they did from the meeting itself because it’s easy to miss the important things or become ‘bigly overwhelmed’ as one bio fund manager explained to me.

Strategically, we’ve taken one specific theme today and explored what we can expect based on what we have learned to date, and looked at how that will potentially impact a few things going forward.

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