Therapy holds back Cancer more than a decade

[Tom.G]

CAR-T-cell therapies involve removing immune cells called T cells from a person with cancer, and genetically altering them so that they produce proteins — called chimeric antigen receptors, or CARs — that recognize cancer cells. The cells are then reinfused into the person, in the hope that they will seek out and destroy tumours.

Initial success rate reported as ≥25% and improving.

Overview:
https://www.nature.com/articles/d41586-022-00241-0

Couldn't find the technical report.

 

[Ygggdrasil]

Couldn't find the technical report.

Decade-long leukaemia remissions with persistence of CD4+ CAR T cells
https://www.nature.com/articles/s41586-021-04390-6

Abstract:

The adoptive transfer of T lymphocytes reprogrammed to target tumour cells has demonstrated potential for treatment of various cancers1,2,3,4,5,6,7. However, little is known about the long-term potential and clonal stability of the infused cells. Here we studied long-lasting CD19-redirected chimeric antigen receptor (CAR) T cells in two patients with chronic lymphocytic leukaemia1,2,3,4 who achieved a complete remission in 2010. CAR T cells remained detectable more than ten years after infusion, with sustained remission in both patients. Notably, a highly activated CD4+ population emerged in both patients, dominating the CAR T cell population at the later time points. This transition was reflected in the stabilization of the clonal make-up of CAR T cells with a repertoire dominated by a small number of clones. Single-cell profiling demonstrated that these long-persisting CD4+ CAR T cells exhibited cytotoxic characteristics along with ongoing functional activation and proliferation. In addition, longitudinal profiling revealed a population of gamma delta CAR T cells that prominently expanded in one patient concomitant with CD8+ CAR T cells during the initial response phase. Our identification and characterization of these unexpected CAR T cell populations provide novel insight into the CAR T cell characteristics associated with anti-cancer response and long-term remission in leukaemia.

 

[jedishrfu]

When I read this news, I felt elated and then thought what about all those who weren't in the study who could have been saved. We lost a dear friend to cancer a few years ago.

Sometimes medical science is heartbreaking.

 

[Laroxe]

CAR-T cell therapies are both complex, time-consuming and expensive, it seems unlikely that they will be widely available as a cancer treatment. Having said that we are currently in the early stages of a medical revolution based on a greater understanding of molecular biology. Many of these new biologic drugs have and are being developed as cancer treatments, several are already widely available, more are being developed and a great deal of research is being done on combinations.
However, the rapid advance of these therapies can make delays seem even more unfair, but it does seem that the so called cancer research "moonshot" is paying off.

 

[Ygggdrasil]

CAR-T cell therapies are both complex, time-consuming and expensive, it seems unlikely that they will be widely available as a cancer treatment. Having said that we are currently in the early stages of a medical revolution based on a greater understanding of molecular biology. Many of these new biologic drugs have and are being developed as cancer treatments, several are already widely available, more are being developed and a great deal of research is being done on combinations.
However, the rapid advance of these therapies can make delays seem even more unfair, but it does seem that the so called cancer research "moonshot" is paying off.

While what you say is true now, it will not necessarily continue to be true in the future. Various companies are working on ways to better automate the processes involved in generating CAR-T cells to make them cheaper and more widely accessible:

In October, Adair demonstrated a new technology she thinks could democratize access to gene therapy. Tweaking a cell-processing device sold by German instrument maker Miltenyi, she mostly automated the process of preparing blood cells with a gene therapy for HIV that her center is also testing. Cells dripped in one end came out the other 30 hours later with little oversight needed. She even added wheels. Adair calls the mobile lab “gene therapy in a box.”

Adair thinks a key job for the mobile gene-therapy lab is to extend experimental studies to the developing world, including Africa, where most HIV cases are. “We wanted to show that we could make the trial mobile, because we are kidding ourselves that treating someone in Seattle is going to have the same risks and outcomes as in South Africa,” she says.

https://www.technologyreview.com/20...n-a-box-could-make-gene-therapy-less-elitist/

 

[Laroxe]

While what you say is true now, it will not necessarily continue to be true in the future. Various companies are working on ways to better automate the processes involved in generating CAR-T cells to make them cheaper and more widely accessible:https://www.technologyreview.com/20...n-a-box-could-make-gene-therapy-less-elitist/

Don't get me wrong here, I think CAR-T cell therapy is an interesting and exiting area of work though to be honest I think its publicity is better than the evidence base.

The idea was first used in treatment of cancer in the early 1990's, but its development has not been an easy one and its use is limited to a small number of haematological cancers. This is despite the huge amount of research devoted to developing the therapies, some 850 CAR-T cell therapies being identified as in development in 2020 while currently only 5 have FDA approval. The use of these 5 come with very specific indications and restrictions.

The initial approval in the U.S. was geared for only about 600 patients a year for specific cancers in young people and while outcome studies look promising we have no reliable outcome data. This is a real cause for concern for a treatment that can cost anywhere between $500,000 to $1000,000 and as most treatments outside of studies are currently paid for privately this unfortunately means that most recipients (87%) in USA are high income and white.

I'm not sure how relevant the work on gene therapy is, it seems to be a quite different technology but the work on universal CAR-T (UCAR-T) cell therapy is in the spotlight and might make a huge difference.

https://ashpublications.org/ashclin...-Cell-Therapies-Predicted-to-Cost-More-Than-1

Unfortunately the problem with controlling the costs is shared by the other new biologic therapies, its estimated that bringing a new one to market can cost in the region of $1.2 billion, a cost that is inevitably passed on. There also appears to be little evidence that pharmaceutical companies are not prepared the use the publicity generated by desperate people facing terminal illness to get the drugs accepted. The issue of cost effectiveness has become a major issue across the world.

My view that other biologic therapies may be more important is based on the very rapid introduction of new drugs that target a range of issues in cancer pathology, so of which being similar to the targets of CAR-T. At the same time because of the numbers being treated it is easier to get more accurate information about the optimal approaches to treatment and reliable outcome figures, the whole process seems to lead to faster developments

This gives a useful overview of CAR-T therapies

https://www.frontiersin.org/articles/10.3389/fimmu.2021.744823/full

 

[Astronuc]

When I read this news, I felt elated and then thought what about all those who weren't in the study who could have been saved. We lost a dear friend to cancer a few years ago.

Any promising development comes 22+ years to late for my youngest brother, but might be helpful for another family member now.

https://www.cancer.org/treatment/tr...reatment-types/immunotherapy/car-t-cell1.html