Dr Bernie Fox (@BernardAFox) is a man on a mission to #FinishCancer, a Twitter hashtag he uses to reflect his vision.
A cancer immunotherapy rockstar, Bernard A Fox, PhD, is the Harder Family Endowed Chair for Cancer Research at Providence Center Center and Chief of the Laboratory of Molecular and Tumor Immunology at the Earle A. Chiles Research Institute in Portland, Oregon.
Fox is also a past president of the Society for Immunotherapy of Cancer (SITC) and CEO of UbiVac, a biotechnology company focused on therapeutic cancer vaccines.
Readers of the Blog and Novel Targets Podcast listeners will recall we had the privilege to interview Dr Fox back at the American Association for Cancer Research (AACR) annual meeting in New Orleans in 2016: “AACR Cancer Immunotherapy Insights from Dr Bernard Fox.”
Fast forward 18 months… it is now time for a detailed update on this issue, as a few interesting events have since come to light in this niche with Genentech/Roche abandoning development of their OX40 agonist, coupled with several new publications from different labs suggesting that concurrent administration of an anti-OX40 antibody with an anti-PD1 antibody attenuated the effect of anti-OX40 and resulted in poor treatment outcomes in mouse models.
Dr Fox kindly spoke to Biotech Strategy Blog about some of the key learnings from this research, where he sees the future potential for OX40, and what his vision for cancer immunotherapy is.
Here’s a short clip from the fireside chat…
He’s definitely a man on a mission to #FinishCancer!
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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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