Yesterday, Juno Therapeutics announced a new deal for a collaboration with Editas Medicine that is:
“Focused on creating chimeric antigen receptor (CAR T) and high-affinity T cell receptor (TCR) therapies to treat cancer. The companies will pursue three research programs together utilizing Editas’ genome editing technologies, including CRISPR/Cas9, with Juno’s CAR and TCR technologies.”
This follows on from their recent deals with Fate Therapeutics and Stage Cell Therapeutics and bluebird bio’s licensing deal with Five Prime for novel antibodies to develop CAR T cell therapy.
One of the most interesting questions in CAR T cell development, is whether you need to incorporate a suicide gene or suicide switch into them that allows you to turn off the response, force the T cells to self-destruct, in the event of severe Cytokine Release Syndrome (CRS) or other serious adverse events.
This review article is another example that straddles data from conferences earlier this month at Immunology 2015 (AAI) and American Society of Gene and Cell Therapy (ASGCT) with the American Society of Clinical Oncology (ASCO) this coming weekend.
At ASGCT we spoke with Dr Carl June and also heard the latest update on what Cellectis are doing from Dr Julianne Smith.
Companies mentioned: Juno Therapeutics, Novartis/U Penn, Cellectis, Bellicum, bluebird bio, Formula, Molmed.
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Some really intriguing news was announced this morning, with Aduro Biotech issuing a press release on their new global collaboration with Novartis for their “immuno-oncology products derived from its proprietary STING-targeted CDN platform technology.”
Many readers will recall Aduro for its program that inserts genetically engineered lysteria into therapeutics aka the LADD regimen. The lead program, CRS–207, in combination with GVAX Pancreas in pancreatic cancer previously received Breakthrough Therapy designation from the FDA. Their scientific advisers include Drew Pardoll and Frank McCormick, who are immunotherapy and protein pathway specialists, respectively.
The collaboration with Novartis is for a completely different platform based on cyclic dinucleotides (CDNs), which are small molecules that are naturally expressed by bacteria and immune cells and have been recently shown to activate the STING (Stimulator of Interferon Genes) signaling pathway in immune cells.
So what’s the significance of this exciting deal and why does it matter?
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This morning we heard that Juno Therapeutics have registered their plans with the SEC for an Initial Public Offering (IPO), highlighting the desire of the VC investors to generate a fast turnaround on their money before a multi-center trial of their CAR-T cell therapy has even started!
One of the challenges with CAR-T cell therapy is despite some stunning results, particularly in pediatric ALL, it remains an experimental one with toxicities that have to been managed. Adult patients, who are extremely sick, have died on trials. If I was at the end of the line faced with certain death, I’d probably roll the dice and take an experimental therapy, but CAR-T cell therapy does have challenges that need to be addressed.
Indeed at the Society for Immunotherapy of Cancer (SITC) meeting last week, one of the Hot Topic sessions that took place after the conference formally ended was in managing the toxicities associated with chimeric antigen receptor T cell (CAR-T) therapy.
Of particular concern for all CAR-T cell therapies in development is severe cytokine release syndrome (sCRS), which requires treatment in hospital intensive care.
Cytokine release syndrome (CRS) involves fevers, hypotension, hypoxia and even neurological toxicities. It’s been known for some time to be a challenging side effect of CAR-T therapy. We first wrote about it at ASH 2012.
As Novartis, Juno and Kite all look towards multi-center registration trials, the identification of patients at risk of severe CRS (sCRS) and the management of this in very sick, often end stage patients remains a real challenge, especially given that we don’t fully know what causes it to occur in some patients, but not others. Patient deaths due to sCRS are not good news on any clinical trial, and even less so when it’s a novel therapy in development.
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.”
Subscribers, whose support helped fund us to go to SITC for the first time, can login below to read more about the 2014 annual meeting at National Harbor, MD or alternatively, you can purchase access via Tinypass by clicking on the blue icon below.
Cellectis is a Paris based biotechnology company, (NYSE alternext: ALCLS.PA) with an aspiring “blue ocean” strategy that, if successful, could revolutionize cancer immunotherapy.
The potential of using engineered T-cells (known as chimeric antigen receptors) to fight cancer was highlighted by the impressive data presented at last year’s annual meeting of the American Society of Hematology (ASH 2013).
To many, the data for the U Penn/Novartis engineered T-Cell therapy (CTL019) in pediatric acute lymphoblastic leukemia (pALL) was worthy of presentation in the plenary session at the meeting.
Over the past year, investors have poured money into companies active in the field: we’ve written about the launch of Juno Therapeutics and their intellectual property (IP) dispute with Novartis. More recently Kite Pharma had a successful IPO.
Why was Biotech Strategy Blog keen to interview Cellectis Chief Scientific Officer (CSO) Philippe Duchateau, PhD and Chief Executive Officer (CEO) André Choulika, PhD (picture left and right respectively)?
The answer is they have a completely new and innovative approach to CAR-T cell therapy that in the long run could be a “game changer.” Their lead product (UCART19) is an allogeneic CAR T cell for ALL and CLL. Allogeneic means the T cells that are modified come from a donor. This is in contrast to the autologous approaches that Kite, Novartis and Juno are developing where the engineered CAR-T cells come from the patient themselves.
All credit to Pfizer for seeing the potential in a company that has been on our radar for a while. They recently announced a major collaboration with Cellectis that could turn both Cellectis and Pfizer into major players in the cancer immunotherapy space.
In this fast moving R&D space there are already signs of where competition to Cellectis may come from, and it’s not Novartis, Juno or Kite.
Subscribers and those with an interest in CAR-T cell immunotherapy can login or sign-up below to read more, including excerpts of the interview at Cellectis HQ in Paris: