It’s Day 7 of our 12 day Countdown to AACR 2016 in New Orleans. After exploring GITR and OX40, we’re now looking at another stimulatory target for cancer immunotherapy: CD40.
We’ve been writing about CD40 as a cancer immunotherapy target for some time. See posts: “CD40 as a Cancer Immunotherapy Target” and “Targeting CD40 in Cancer Immunotherapy.”
Anti-CD40 antibodies are agonists that act on stimulatory signalling receptors on T cells and antigen presenting cells (APCs). Targeting CD40 effectively acts to “put the foot on the gas” and may help generate a better immune response. This could be important in cancers that have fewer natural T cells present.
CD40 is an attractive target because it’s expressed in more than 50% of carcinomas and melanomas and almost all hematological B cell malignancies. Of particular interest is the potential to combine a CD40 agonist with a PD-1/PD-L1 checkpoint inhibitor.
Multiple companies have CD40 agonists in clinical development including Roche, Apexigen, Alligator Biosciences and Seattle Genetics. There are others coming too.
In this preview of AACR 2016, we’re looking at the CD40 landscape. New products and companies have entered the scene, so we’re highlighting them and some of the CD40 presentations to look out for at AACR 2016 (and why they matter).
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There are now several CD40 agonist antibodies in early clinical development from several different companies, including:
- Roche – RO7009789
- Apexigen – APX005M
- Seattle Genetics – SEA-CD40
- Alligator Bioscience – ADC–1013
This post is the last in our cancer immunotherapy coverage from the European Cancer Congress in Vienna. It features excerpts from an interview with Dr Christian Rommel, head of oncology discovery at Roche in Basle, Switzerland in which he talks about the development of their CD40 monoclonal antibody. Readers may recall we wrote about this from SITC 2014 last year: “Targeting CD40 in Cancer Immunotherapy.”
This post is also a new primer on CD40 as we start our coverage of the Society for Immunotherapy of Cancer (SITC) 2015 annual meeting. We’re informed by SITC it’s a sell out conference with 600 more people than last year’s record breaking number. Cancer Immunotherapy is indeed the hottest topic in cancer drug development.
If you have plans to be at National Harbor this week, we hope to see you there!
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One of the interesting questions raised by the recently announced and much-discussed Juno/Celgene collaboration is whether you really need a Chimeric Antigen Receptor (CAR) T cell therapy in your portfolio to succeed as a global cancer immunotherapy company?
One leading cancer immunotherapy company that believes you don’t is Roche. At ASCO 2015 I had the privilege to talk about this with a leading cancer scientist, William Pao, MD PhD (pictured below). Dr Pao formerly worked with Nobel Prize-winning scientist Harold Varmus at Memorial Sloan Kettering, and subsequently led the Hematology-Oncology Division at Vanderbilt. He joined Roche in July 2014 to lead their early development of innovative oncology new products (see press release).
I particularly enjoyed Dr Pao’s discussion of the T-cell centric strategic framework around which the Roche/Genentech cancer immunotherapy portfolio strategy is based.
If you haven’t done so already, do listen to Episode 3 of the Novel Targets podcast (ASCO Lung Cancer Show) in which you can hear an excerpt from my interview with Dr Pao.
This is the first in a series of interviews with scientific leaders at companies at the forefront of cancer research.
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We know from preclinical research that immunosuppressive tumour microenvironments can restrain anti-tumour immunity, thereby making subsequent therapeutic interventions less effective than expected. CD40 activation has been shown to reverse immune suppression and drive antitumor T cell responses, which in turn could lead to potentially better outcomes.
What happens when patients with advanced melanoma are given a checkpoint inhibitor plus an immune agonist such as anti-CD40?
Can we help the non-responding patients to checkpoint blockade improve their outcomes and shift the long tail in survival curves up using this approach?
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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.
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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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