For the final postcard in our 2020 summer mini-series on the potential of immunometabolism in oncology R&D, we’re taking an in-depth look at the ways in which metabolic programming can overcome immunosuppression in the tumour microenvironment (TME), as well as looking at additional novel ways in which the fitness of T cells can be impacted.
We’ve already covered glutaminase, arginine, p38 and others, yet there are other metabolic effects to consider too, as we discover in our latest expert interview. In the penultimate postcard, we looked at mitochondrial phenotypes and how they can impact both mitochondrial and T cell fitness, which are important aspects in making adoptive cell therapy (ACT) based approaches such as TILs and CAR-T cell therapies more effective.
Deep thoughts on immunometabolism and how it can impact antitumour response
These themes show up yet again, but in a rather different context because T cell fitness can also impact immune checkpoint blockade, oncogenic targeting, as well as transcriptional and epigenetic approaches.
As much as we have been slowing building up the evidence during this series, in the finale it’s now time to kick up things up a notch or two and draw some unifying ideas together.
We accomplish this feat with a rising young star in this particular niche, Dr Ping-Chih Ho, who is at the University of Lausanne.
He kindly spoke to BSB about his pioneering and prolific research, some of the critical questions he has sought to answer, plus what he sees are important future directions to consider in metabolism research.
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What do T cells want?
In the third post in our summer mini-series on immunometabolism, we’re continuing our journey by taking a look at glutamine as a target, and in particular, the potential of glutaminase inhibitors.
Cancer cells compete with immune cells for glucose and glutamine in the tumor microenvironment, and if the cancer cell wins then immuno-surveillance and anti-tumour immune response can be diminished. Of interest, glutamine addiction is commonly seen in cultured cancer cells.
This begs a critical question – can we target glutamine therapeutically in patients, and if so, what happens?
In this article we highlight an expert interview with Dr Jeffrey Rathmell, who is Professor of Pathology, Microbiology and Immunology at Vanderbilt, where he directs the Vanderbilt Center for Immunobiology.
Dr Rathmell is at the forefront of research into T cell fuels such as glutamine and has published preclinical work on early compounds in this niche, including Calithera’s glutaminase inhibitor, CB-839, for example.
He kindly spoke to BSB after the AACR20 virtual annual meeting where he chaired a session on Metabolism and the Tumor Microenvironment.
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The B-cell maturation antigen (BCMA) is an oncogenic protein target relevant to multiple myeloma that we have been following for a while on BSB, including an expert interview with a global myeloma KOL at ASH last December as part of a wide ranging discussion and deeper look at the Future of Multiple Myeloma.
This weekend I was following a myeloma workshop where quite a bit of teasing early data was presented that may give us clues about what’s likely to be interesting at ASH18.
I wasn’t the only one doing this judging by a raft of reader questions that came in, particularly on the topic of BCMA and other emerging targets in this disease.
Is one BCMA better or worse than another? Will antibodies take a BiTE out of the CAR-T cell therapy noise? We take a careful look at these issues to explore what’s what and what really matters in this niche.
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Some people may think that if you just give a whole boat load of engineered T cells, and in particular, those modified with a Chimeric Antigen Receptor (CAR), that responders are “cured.”
While some recipients of engineered T cells can have long-term, durable remissions, others may initially respond, only to subsequently relapse.
Resistance to CAR T cell therapy can and does occur.
In this post, we talked with a leading expert about the latest research on how resistance to cell therapy develops, and the potential strategies to overcome it.
CAR T cell therapy is exciting, but remains an emerging field with multiple ways in which the competitive landscape may be shaped moving forwards.
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That’s the $64K question we all want to know, and what’s more is gene editing necessary when it comes to creating an “off-the-shelf” T cell therapy, which instead of modifying a patient’s own T cells (autologous), uses cells from a healthy donor (allogeneic)?
We were really curious too, and sought out one of the world’s leading experts for their opinion on this very issue.
Subscribers can login to read more, along with our analysis of the potential impact of this latest news on CAR T cell therapies.
It remains exciting times in cancer immunotherapy with breakthrough new cell therapies and checkpoint inhibitors that enhance the effectiveness of T cells.
Last Friday, Paris based Cellectis filed their IPO registration statement with the Securities and Exchange Commission (Link to F-1).
They plan to raise $115M through an offering of American Depository Shares. You can read more about their allogeneic Chimeric Antigen Receptor (CAR) T cell approach in the two interviews we did with senior management last year.
Here’s an excerpt of the interview Cellectis CEO André Choulika, PhD gave Biotech Strategy Blog last year – it was the No1 post in 2014: Can Cellectis Revolutionize CAR-T cell Immunotherapy?
As multiple companies seek to move CAR-T cell therapies forward in clinical trials, what will be interesting to see is how this novel treatment fits in with existing therapies such as bone marrow transplants. Will it replace them, or be a bridge to a transplant that enables relapsed or refractory patients to have a second chance?
In addition, where are the potential opportunities beyond B-cell malignancies such as acute lymphoid leukemia (ALL) where there’s been dramatic success, particularly in children?
Last week Biotech Strategy Blog had the privilege to interview Dr Krishna Komanduri who is Director of the Adult Stem Cell Transplant Program at the University of Miami Sylvester Cancer Center and holds the Kalish Family Chair in Stem Cell Transplantation.
A physician scientist, he exudes a sense of calm professionalism – I am sure this must reassure many of his patients. Having a bone marrow transplant has been likened to jumping off a cliff in terms of what it does to one’s immune system.
In the last 2-3 years, he has dramatically increased the number of transplants at the University of Miami Sylvester Cancer Center.
Dr Komanduri (@DrKomanduri) was co-chair of the 2015 BMT Tandem meeting that took place earlier this month in San Diego. It’s the combined annual meeting of the American Society of Blood and Marrow Transplantation (ASMBT) and the Center for International Blood and Marrow Transplant Research (CIBMTR).
In a half hour interview he shared his thoughts on what was exciting at Tandem, where the field is going and some of the best abstracts at the meeting which included data on CAR-T cell therapy, GVHD and gene therapy.
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