At the recent 2014 annual meeting of the Society for Immunotherapy of Cancer (SITC), it was surprising to see how many people stayed till the bitter end of the conference to attend the Hot Topic Symposium on Accelerating Tumor Immunity with Agonist Antibodies.
Readers are well aware of the potential of cancer immunotherapies that block immune checkpoint receptors. After all, the FDA has already approved antibodies that block CTLA–4 (ipiliimumab) and PD–1 (pembrolizumab) in metastatic melanoma, with nivolumab (Opdivo) currently being reviewed for advanced melanoma and lung cancers.
These antagonists, and others in development targeting the PD-L1 signalling pathway, such as MEDI4736 and MPDL3280A, act to reduce the engagement of inhibitory receptors on the T-cell. This results in a releasing of a brake on the T cell response, enabling killer T cells to attack the tumour(s).
CD40 in cancer Source: Costello et al., 1999
However, in order to stimulate an immune response, particularly in tumors with few natural T cells, it is likely that agonist antibodies will be required that act on stimulatory signalling receptors on T cells and antigen presenting cells (APC’s).
In a previous post from SITC, we discussed the potential of agonists targeting OX40, and the rational for combining an anti-OX40 antibody with an anti-PDL1. This is one of the hottest targets that thought leaders are excited about from our discussions.
It isn’t the only one of interest though. Another potential stimulatory target that might be suitable for combination with anti-PD–1/PD-L1 is an antibody against CD40 (not to be confused with OX40). The pathway (shown right) is quite complex.
Subscribers can login to read more about another fascinating talk from SITC 2014 on where the cancer immunotherapy may be heading.
There has been a lot of enthusiasm in the immuno-oncology space since ASCO about the possibility of combining a checkpoint inhibitor with an immune stimulator. There are several ideas behind this approach since:
a) Not all patients respond to checkpoint inhibitors
b) Some patients only partially respond, although they can achieve an attenuated response before relapsing
An important question in many people’s mind is what is different about these subsets of patients compared to exceptional responders? How can we change that situation for the better?
Two approaches that have been mooted of late include the following:
- Using a cancer vaccine to ‘prime’ the tumour
- Combining a checkpoint inhibitor with an antibody agonist to stimulate the immune system
At SITC in Maryland this weekend, there were plenty of packed presentations and discussions on both of these classes of agents, so this is a good time to explore the idea of immune stimulators further based on the latest data we heard.
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National Harbor, MD – The 2014 Society for Immunotherapy of Cancer (SITC) annual meeting officially kicked off today, with a record-breaking 1,500 attendees. The organization has grown by 33% over the past year highlighting the explosive progress in the field, and the growing importance of SITC!
There was a lot of thought provoking science on display as researchers and translational scientists came from all around the world to share results and talk about the future.
What struck me at the meeting today was the collegiality and friendliness of all who are here. It’s exciting times in immunotherapy and immuno-oncology and everyone at the meeting is bound by a common goal of making a difference to the lives of cancer patients.
The President of SITC, Francesco Marincola (Sidra) quoted Winston Churchill in his introductory address:
“Now this is not the end.
It is not even the beginning of the end.
But, perhaps it is the end of the beginning.”
Dr Marincola’s choice of quote seemed to strike the right balance of where we are at today: there’s still a long way to go to optimize cancer immunotherapy treatments, but equally there’s been tremendous progress to reach the point we are at where there are durable long-term responses in many patients who would otherwise not be alive today.
What was the highlight of Day 1 of SITC 2014?
For me, this morning, it was the presentation by Marcel van den Brink (MSKCC) on the influence of the microbiome on graft-versus-host disease (GvHD) for which there’s been no effective new treatment for over 25 years:
In the afternoon, it was the presentation by Roy Herbst (Yale) on the top ten lessons learned about immunotherapy for NSCLC.
It’s unfair to single out two presenters when there were multiple presentations and posters of note, but they stood out for me. If you’d like to read our more detailed notes from the road after Day 1 of SITC 2014, do log-in if you are already a subscriber.
The Society for Immunotherapy of Cancer (SITC) annual meeting promises to be a most interesting one, if the first day is anything to go by. It’s being held this week at National Harbor, Maryland on the banks of the Potomac River just south of Washington DC.
As the meeting started with some intensive workshops yesterday, the American Society for Hematology (ASH) annual meeting abstracts were released at 9am, giving up a choice between writing up SITC in situ or switching gears and analysing the initial hematology abstracts. In the interests of sanity, we have decided to focus on SITC for the next week, then move onto the AACR-NCI-EORTC conference, before reviewing the ASH data in detailed previews.
SITC is mostly a translational science meeting with a little bit of relevant clinical data through in here and there. It’s also not for the faint hearted, especially given the sheer intensity and pace of some of the talks – keeping up with pen and paper to hastily scribble notes is surprisingly quite hard!
It was an honour to attend as one of the few members of the media here. The excitement is palpable, with speakers reminding us of how only a few years ago, few people attended immunotherapy sessions at ASCO. SITC is rapidly becoming a major meeting with a record-breaking 1500 expected for the first time! It is the immuno-oncology meeting to attend for those interested in understanding the emerging trends, landscape and direction that research is taking us.
Yesterday SITC fielded two workshops with impressive line-ups from the immuno-oncology space that included Drs Carl June, James Allison, Tom Gajewski, Susan Topalian, Stephen Hodi and Mario Sznol, to name a few. The workshops focused on different topics:
- A basic one on understanding the immune system
- A more advanced one on combination strategies in immunotherapy
Rather than summarise all the talks from both sessions that ran a full day each, we’ve decided to focus on some themes, ideas and concepts that catch our attention each day. Here’s the first of our daily reviews from the SITC 2014 annual meeting. Thanks to all our subscribers whose support enabled us to attend this meeting for the first time.
To learn more about our impressions from the SITC immunotherapy workshops yesterday, you can log-in.
This week sees the start of the 2014 annual meeting of the Society for Immunotherapy of Cancer (SITC) at National Harbor, MD.
Given the rapid progress that is taking place in the field of cancer immunotherapy, we’re excited to be flying up to DC to attend the meeting for the first time as part of our conference coverage.
Many of the leading translational scientists in immuno-oncology will be at SITC to discuss the current landscape, challenges and opportunities.
For all the promising results we’ve seen so far, harnessing the body’s immune system to fight cancer is very much a work a progress.
Don’t expect much from SITC on social media, most of the data is likely to be unpublished, which is why you have to go to meetings like SITC, ARVO and AACR in person. An important part of attending is the in-person conversations and connections that take place.
You can download the preliminary program on the SITC 2014 Annual meeting website. There’s also an iphone/android app for those attending.
- Addresses by the 2014 Richard V. Smalley, MD Memorial Award recipient, Giorgio Trinchieri, MD – National Cancer Institute and the Annual Meeting keynote speaker, Olivera J. Finn, PhD – University of Pittsburgh
- News on important initiatives and updates in cancer immunotherapy by key stakeholders in the field
- Workshop on Combination Immunotherapy: Where Do We Go From Here?
- Primer on Tumor Immunology and Cancer Immunotherapy™
- Hot Topic Symposia on Managing Engineered T-Cell Toxicities & Accelerating Tumor Immunity with Agonist Antibodies.
If you haven’t already seen it, this educational video from Roche/Genentech, narrated by Dan Chen MD PhD (Cancer Immunotherapy Franchise Head) is not only educational in discussing the mechanism of action of their anti-PDL1 monoclonal antibody, MPDL3280A, but is highly fun and entertaining to watch. Enjoy!
Sally interviewed Dr Chen at ASCO this year for a blog post from the meeting on “Making a difference in advanced bladder cancer.”
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