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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Having heard about a one day symposium on immunotherapy organised by Charles River, I headed over to Munich and the EORTC-NCI-AACR conference a day early… Providentially it seems, as the Lufthansa strike will likely affect a few travellers en route to the Triple and ASH/WCLC/SABCS conferences.
The focus of this excellent one day event was on ‘Mapping the future of cancer drug discovery.’
So what stood out as interesting and intriguing?
Quite a few things, as it turned out, including a novel target in cancer research that I haven’t come across before.
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National Harbor, MD
Despite remarkable results with cancer immunotherapy to date, we do need to keep out feet on the ground and remember that response rates are relatively low to modest (10–30%) and the majority of patients do not respond or see a benefit with these approaches.
As we start moving beyond checkpoint monotherapy, the realisation has fast hit many researchers and companies that we really don’t know as much about the tumour microenvironment (TME) as we would like.
No doubt we will learn a lot more about it from the combinatory approaches, but be aware that this also means higher risk associated with such developments – we will likely see a lot of failures – and hopefully, some successes too.
This is where the little biotech companies have an opportunity to shine… they may have some intriguing IO compounds in development but not an anti-PD1/L1 backbone, meaning they can collaborate with a big pharma company to explore novel combinations in small phase 1/2 trials to determine what works or not. This is much lower risk (and R&D costs) for both parties and we get to see more quickly where things shake out.
At the annual Society for Immunotherapy of Cancer (SITC) meeting last week, there was a whole day devoted to New Immunotherapy Drug Development.
Some of these agents look worthy of watching out for and following their progress. A variety of data in different targets and MOA were presented from big and small companies alike. We selected a few of the promising ones for further review and discussion.
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It’s Day 4 of our Road to AACR 2016 mini-series
In the run up to the start of the annual meeting of the American Association for Cancer Research (AACR) that takes place in New Orleans from April 16 -20, we’re highlighting some of the hot topics and interesting targets with data to be presented at the meeting (Twitter #AACR16).
We’ll be providing conference coverage from AACR both during and after the meeting. The program this year offers a veritable smorgasbord of choices, particularly in cancer immunotherapy. It’s going to be hard to cover every session we want to attend!
AACR will be webcasting many presentations, however, much of the work presented and discussed at AACR is unpublished and/or still a work in progress, so do check if a talk you are interested in will be webcast or not. The online meeting calendar indicates whether permission has been given and if all the slides will be included. If you really want to hear something do get to meeting rooms early; we expect the cancer immunotherapy sessions will be especially popular!
In today’s post we’re looking at what’s new at AACR 2016 for cancer immunotherapies that target IDO1 and TDO and their downstream effectors.
Tumor cells and myeloid cells in the microenvironment express high levels of indoleamine-2,3-dioxygenase 1 (IDO1). IDO1 is a rate-limiting enzyme in the degradation of the amino acid tryptophan (TRP). Depletion of tryptophan inhibits T cell responses.
Another route by which the tryptophan metabolic pathway can lead to immunosuppression is via the enzyme TRP-2,3-dioxygenase 2 (TDO), which may be an additional target for cancer immunotherapy. Some IDO1 inhibitors also inhibit TDO, others don’t, which makes for an interesting question as to whether you need a dual-targeted approach or not?
In this post we’re looking at:
- Some of the companies who have IDO1/TDO inhibitors in development – there is a surprising amount of activity!
- What is the right combination partner?
- Who is most likely to benefit from IDO1/TDO cancer immunotherapy?
Data at AACR 2016 may help us answer some of the above questions, and we’ve showcased a few of the relevant sessions and presentations for your AACR “dance card” if this is an area of interest.
Subscribers can login to read more or you can purchase access. This post is Day 4 of our Road to AACR 2016 mini-series.