Cellular immunotherapy with Natural Killer (NK) cells is emerging as a potentially effective treatment option for older patients (more than 60 years of age) with Acute Myeloid Leukemia (AML).
AML remains a disease with high unmet medical need, particular for those patients who relapse and are ineligible for a stem cell transplant (SCT).
There’s considerable buzz around adoptive cellular therapy and, in particular, chimeric antigen receptor modified T cells (CAR T cells). It is important, however, to note that there are other approaches worthy of consideration. See post: Could a Novel Cell Therapy replace CAR T cell therapy?
Cancer immunotherapy targeting NK cells has already shown some early promising results in AML. We await the read out of the EFFIKIR trial data for lirilumab (Innate Pharma/BMS), an anti KIR (killer inhibitory receptor monoclonal antibody. See post: Innate Pharma at an Inflexion Point, an interview with Hervé Brailly.
Rizwan Romee, Maximilian Rosario, Melissa Berrien-Elliott and colleagues at the Washington University School of Medicine in St Louis (@WUSTLmed) recently published the results of a clinical trial with a novel NK cell therapy: “Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia.”
The paper was published on 21 September, 2016 in Science Translational Medicine (link).
To better understand the trial results and what they tell us about NK cell therapy in AML, BSB spoke with one of the joint first authors, Melissa Berrien-Elliot, PhD (pictured right) and senior author, Todd A Fehniger MD PhD, Associate Professor of Medicine at Washington University.
This post is part of our series on the innate immune system.
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Acute Myeloid Leukemia (AML) is challenging disease to treat and quite distinctly different from its cousin, acute lymphoblastic leukemia (ALL). The first is more common in adults, while the second is more prevalent in children. Success rates with pediatric ALL have far outstripped what we have achieved with adults in AML to date, partly due to the elderly nature of the disease making for poorer outcomes with stem cell transplants (SCT), as well as increased clonal heterogeneity and cytogenetic complexity with age.
Quite a few FLT3 inhibitors have come and gone over the years – many keen observers will remember Cephalon’s (now Teva) TKI called CEP-701, which was tested in relapsed/refractory disease and Elderly AML, for example, and slid off largely unnoticed to dog drug heaven.
How much does clinical trial design impact a drug’s success or failure?
Sometimes quite a bit, as this story with midostaurin demonstrates; limited activity in advanced disease but much more dramatic results in the upfront setting. Clearly, sometimes testing drugs in later disease does not predict their future performance elsewhere!
To put more colour on the data presented at ASH, we interviewed a thought leader in adult AML for his perspective on the FLT3 R&D developments.
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Much has been written about the success of checkpoint blockade in solid tumours over the last couple of years with the advent of anti-CTLA4 therapy (ipilimumab/Yervoy) for metastatic melanoma followed by the more recent approval of the anti-PD-1 antibodies in advanced melanoma (pembrolizumab/Keytruda and nivolumab/Opdivo) and lung cancer (nivolumab).
What about hematologic malignancies though?
At the recent American Society of Hematology (ASH) conference, we heard about the first clinical data for anti-PD1 antibodies in patients with refractory classic Hodgkins Lymphomas (cHL) and saw some impressive results. Interestingly, though, the early preclinical work was conducted in mice looking at CTLA4 blockade in a variety of tumours, both solid and liquid.
Is there a rationale for targeting CTLA4 in leukemias, lymphomas and even myeloma? New data presented at a medical meeting in patients with heavily pre-treated and relapsed disease post stem cell transplantation suggests that this might be feasible.
Check out to today’s article to learn more about this clinical opportunity in more detail – you can log in or subscribe in the box below.
The 2015 Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT 2015) was held in Istanbul from March 22-25, where it offered a European perspective on some of the latest developments in cancer immunotherapy.
We’ve heard a lot in the United States about the early CAR T cell therapy clinical trial results from institutions such as UPenn, CHOP, MSKCC, Fred Hutchinson, Seattle Children’s, the NCI, and MD Anderson to name but a few, so it was good to see a leading a European center join the club: University College London (UCL).
While completing a Masters degree in Human and Applied Physiology at King’s College London, I spent several weeks training at UCL and particularly enjoyed the intercollegiality of the University of London.
At EBMT15, Dr Sara Ghorashian Clinical Training Fellow at the Insitute of Child Health at UCL, presented data on a phase 1 trial of Epstein Barr virus (EBV) specific T cells transduced with a first generation CD19 Chimeric Antigen Receptor (CAR). The trial data was first reported by Dr Ghorashian (pictured below) in an oral presentation at #ASH14 (Abstract 383).
Dr Ghorashian stated at EBMT that UCL have several CAR T cell therapy trials planned.
Readers will be aware that earlier this year that UCL spun-off a series A funded company, Autolus, to commercialize their CAR T cell therapy research.
Although £30m from Syncona (a subsidiary of the Wellcome Trust) is not a lot of money by US investment standards, UCL is nonetheless a European center to watch if you have an interest in the CAR-T competitive landscape.
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The announcement earlier this week that Cellular Biomedicine Group (NASDAQ: CBMG) has acquired rights to the Chimeric Antigen Receptor T cell (CAR-T) therapy of the PLA General Hospital in Beijing (pictured right) should come as no surprise to industry watchers. (Link to Press Release).
The share price in $CBMG has risen from $16.31 on February 4 to $23.60 as of close of business on Feb 10, 2015 in what looks like a poorly kept secret! It looks like most of the rise in share price took place immediately prior to the company’s formal Feb 9, 2015 announcement of the Chinese deal.
Those following the cancer immunotherapy space have known for some time that several Chinese groups are working on CAR-T cell therapies that could be a threat if licensed or acquired.
Given the significant investor interest in this space, which is almost bordering on “tulip mania,” it’s entirely foreseeable that companies looking to share in this opportunity would go looking towards China.
One investor on Twitter in response to this news asked should Chinese data be trusted?
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After last week’s post on therapeutic tumor infiltrating lymphocytes (TILs), we received a bunch of questions from readers.
I don’t have time to answer them all in detail individually (sorry!), but it does provide an opportunity to review the evolving landscape and address some of them within the latest article.
It seems to be a good time to take a broader look at T cell manipulation, especially as it pertains to the application of TILs, chimeric antigen receptors (CAR), and T cell receptors (TCR).
We’ve certainly come along way since the historic lecture in 1991 pictured right (photo: National Institutes of Health), but there’s still some way to go before the full potential of cancer immunotherapy is reached.
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Over the last two years we’ve written extensively about chimeric antigen receptor (CAR) T cell therapies, checkpoint inhibitors and immune agonists (stimulants), yet these aren’t the only novel immunotherapies that are being developed to target cancer cells.
One area that hasn’t received a lot of attention is adoptive cell transfer (ACT) and therapeutic tumour infiltrating lymphocytes (TILs).
- What exactly are these approaches and what progress has taken place so far?
- Where is this field going in the near future?
To answer these questions, we put together a primer based on the groundbreaking research of Dr Steven Rosenberg (NCI Surgical Branch), and his invited talk at the recent American Society of Hematology (ASH) meeting.
As Rosenberg himself noted, what they’re doing is pretty daunting and yet, results so far have shown some impressive responses in some patients, especially those with metastatic melanoma, but other cancers have also responded well to this novel approach.
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Several subscribers have written to ask what we think of Houston based Bellicum Pharmaceuticals?
Bellicum is a company that along with Novartis, Kite, Juno and Cellectis has a Chimeric Antigen Receptor (CAR) T cell therapy in development, amongst other things.
Readers already know the company had a successful IPO in December (NASDAQ: BLCM) and were reported to have raised $140M to fund future development.
This morning, the company announced enrollment of the first cohort of pediatric patients in a phase 1/2 dose escalation trial of BPX-501 (link to press release). This T cell therapy aims to mitigate the risk of graft versus host disease (GvHD) after an allogeneic haploid hematopoietic stem cell transplant.
BSB spoke with Bellicum CEO Tom Farrell and COO Dr Annemarie Moseley to answer some of the questions we think subscribers would like to know more about such as:
- Market opportunity for BPX-501
- Mechanism of action of BPX-501
- Strategic direction the company is taking
- Vision with regards to its CAR-T development
- Milestones expected in 2015
We’ve provided some additional commentary on the challenges and opportunities Bellicum may face in the GvHD market and how we think the company stacks up against the competition in the CAR-T space. Be warned this piece is a long read: 6,000+ words!
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Picture Credit: @gene_antibody
For much of the last two years, one of the hottest topics around has been T cell manipulation, which can happen in many different forms.
This is just one area that we have covered extensively in the immuno-oncology space from Chimeric Antigen Receptor (CAR) T cell therapies to checkpoint inhibitors, as well as various antibodies, including the first bispecific T-cell engager (BiTE) to CD19 that recently approved by the FDA called blinatumomab (Blincyto) from Amgen.
Not all cancer patients respond to all these approaches though.
Why is that and what approaches or novel targets can we explore next to address this vexing issue?
At the SITC and SABCS meetings, I saw some really interesting and unusual presentations, together with some recent publications on topic, that really piqued my interest in this challenge. They are early signs of the new directions some of the research in this field could go. Overcoming resistance and understanding different aspects of immune escape will likely be very instructive in developing the next generation of combination studies that could make a positive impact on patients.
Today’s post touches on some of these exciting developments and includes an in-depth interview with Dr Ira Mellman, the scientist behind Genentech’s immunology research program at gRED.
Interested readers can sign in or sign-up in the box below to read more about the exciting new developments that are happening with different types of antibodies in the immuno-oncology space.
Readers don’t need Biotech Strategy Blog to tell them that Chimeric Antigen Receptor (CAR) T cell therapy (CAR-T), along with Checkpoint blockade, is one of the hottest areas of cancer drug development.
The last two days have seen pre #JPM15 deal activity with Kite Pharmaceuticals ($KITE) announcing a commercial collaboration with Amgen ($AMGN), which is not surprising given several of the Kite senior management team previously worked at the company.
Meanwhile, both Seattle based Juno Therapeutics ($JUNO) and Houston based Bellicum Pharmaceuticals ($BLCM) had successful IPO’s at the end of 2014. Interestingly, Bellicum are initially focusing most of their IPO funds, not on bringing their CAR-T to market, but on a novel cell therapy post stem cell transplant that aims to lower graft versus host disease (GvHD). GvHD is something we’ve been writing about regularly here!
Just this morning we’ve seen yet more CAR-T activity, with European Cardio3Biosciences (Euronext Brussels and Paris: CARD) acquiring the CAR-T technology of Oncyte (the oncology division of privately-held U.S. biotechnology company Celdara Medical).
There’s certainly a lot of activity in the CAR-T space and I expect we will hear more at next week’s JP Morgan Healthcare conference in San Francisco (#JPM15). One player in the CAR-T space who has not been gaining as much attention, and one that I think should not be dismissed, is Paris based Cellectis (Alternext: ALCLS.PA), who struck deals with both Servier and Pfizer last year. In June, BSB went to Paris and interviewed Chairman and CEO André Choulika, PhD and CSO Philippe Duchateau, PhD. At the recent American Society of Hematology (ASH) annual meeting in San Francisco, Julianne Smith, PhD (pictured below), Vice President CART Development at Cellectis, gave an in-depth interview to BSB. Some key questions to address here are what are some of the important milestones for Cellectis in 2015 and and what makes the Cellectis CAR-T approach different from other companies in this space? Update Nov 7: This post now has two updates relating to the important news that came out after this post was published concerning the issuance by the USPTO of a gene editing patent that covers Cellectis’ intellectual property. Subscribers can login to read more or you can purchase access by clicking on the blue icon below.