#CARTCells

In München und Singapur werkelt das #Startup Eximmium an neuen Antikörpern gegen #Krebs – und macht sich dabei ein ungeklärtes Phänomen von Krebszellen zunutze. @InsertCaffeine erklärt uns das Ganze genauer: https://www.laborjournal.de/editorials/3231.php #Biotech #CarTCells #Antikörper

'A year ago, Caribou Biotherapeutics’ CEO was telling Fierce Biotech that the company’s natural killer (NK) cell therapy program was the “tip of the spear” for its solid tumor strategy and there were no plans to pause this work to conserve cash.
Now, with the biotech eyeing up ways to keep the money flowing into 2026, the CRISPR-focused company has decided that the preclinical CAR-NK research needs to go—along with 12% of Caribou’s workforce'
#Immunotherapy #Immunology #CARTcells
https://www.fiercebiotech.com/biotech/caribou-cuts-nk-cell-therapy-program-lays-12-staff-fund-car-t-priorities

'Twenty-nine different Car-T treatments for autoimmune diseases, ranging from the muscle inflammation condition myositis to multiple sclerosis, are now being tested in clinical trials by drugmakers including Novartis and Bristol Myers Squibb'

#Immunology #Autoimmunity #CARTcells

https://www.ft.com/content/a974f4c1-bb8a-4a1b-9d88-a2cf14be5c6e

'These studies have helped to answer “some of the questions that were precipitated by the FDA announcement,” Maus said. They still have not found definitive evidence that CAR-T therapy has directly caused new cancers, she said, and scientists continue to suspect that such an event would be extremely rare.'
#Immunology #Immunotherapy #CARTcells
https://www.statnews.com/2024/07/12/cancer-car-t-therapy-fda-secondary-cancers/?utm_campaign=rss

'Even without exposure to antigens, some CARs increase proliferation and nutrient uptake in T cells. Using stable isotope tracers and mass spectrometry, we observed basal metabolic fluxes through glycolysis doubling and amino acid uptake overtaking anaplerosis in CAR-T cells harbouring a rituximab scFv, unlike other similar anti-CD20 scFvs.'
#Immunology #Immunotherapy #CARTcells
https://www.nature.com/articles/s42255-024-01034-7

'However, the established use of viral vectors for genetic engineering of CAR immune cells is still subject to particular safety concerns and requires further improvements. 1 Consequently, non-viral methods for immune cell engineering are gaining increasing interest. In this context, transposon-based technologies represent a promising alternative engineering technology that enables safe genomic insertions of large cargo, such as multi-cistronic CAR-expression cassettes, using fast and cost-effective manufacturing processes '
#Immunology #Immunotherapy #CARTcells
https://www.cell.com/molecular-therapy-family/molecular-therapy/abstract/S1525-0016(24)00325-3?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1525001624003253%3Fshowall%3Dtrue

" The insights derived from this analysis do not only support a CD19 CAR T cell-mediated reset of the memory B cell compartment, but also the parallel inhibition of the interferon signature
in #monocytes and #Tcells of #SLE patients"

https://insight.jci.org/articles/view/179433

Striking that this apparently works better in getting rid of certain memory #Bcells than anti-CD20 antibodies.

#scRNAseq #TCR #carTcells #OpenAccess #science

'Although T cell depletion was greatly enhanced by CD47 blockade in our studies, our data demonstrate that macrophage phagocytosis limits the persistence of adoptively transferred T cells even in the absence of CD47–SIRPα blockade'
#Immunotherapy #Immunology #CARTcells
https://www.nature.com/articles/s41586-024-07443-8#Sec10

'Our results reveal an increased sensitivity of low affinity CAR-T cells to PD-L1-mediated inhibition when compared to their high affinity counterparts by using in vitro models of tumor cell lines and supported lipid bilayers modified to display varying PD-L1 densities.'
#Immunology #Immunotherapy #CARTcells
https://www.nature.com/articles/s41467-024-47799-z

'Although the information provided by the FDA was thin at the time, the agency told reporters that it had observed 20 cases in which immune-cell cancers known as lymphomas had developed in people treated with CAR T cells. Levine, who is a co-inventor of Kymriah, the first CAR-T-cell therapy to be approved, started jotting down questions. Who were these patients? How many were there? And what other drugs had they received before having CAR-T-cell therapy?'

#Immunology #Immunotherapy #CARTcells

https://www.nature.com/articles/d41586-024-01215-0

"Plenge and colleagues are laying out a three-part plan to tackle autoimmune diseases of all types. Under this vision, ‘step one’ drugs — including many available small molecules and antibodies — would be used to control the inflammation that marks these disease. ‘Step two’ drugs, exemplified by CAR Ts, could be used to reset the immune system by taking out the pathogenic immune cells that drive the inflammation. And ‘step three’ drugs could promote homeostasis and the repair of any lasting damage."
#Immunology #Autoimmunity #AutoimmuneDisease #Immunotherapy #CARTcells
https://www.nature.com/articles/d41573-024-00069-5

'In Brazil, the Oswaldo Cruz Foundation, a vaccine manufacturer and the largest biomedical research institute in Latin America, recently partnered with a US-based nonprofit called Caring Cross to help develop local CAR-T manufacturing capabilities. Caring Cross has developed a point-of-care manufacturing process able to generate CAR-T therapies for an even lower cost—roughly $20,000 in materials and $10,000 in labor and facilities.'
#Immunology #Immunotherapy #CARTcells

https://www.technologyreview.com/2024/04/12/1091161/car-t-cancer-therapy-treatment-expense/

The art of war:

"Pulling from cancer’s playbook, Roybal and his colleagues incorporated 71 mutations, found in cancerous T cells, into CAR T cells. When they looked at how these perturbations affected T-cell function, one mutation stood out. The CAR T cells carrying an aberrant protein dubbed CARD11–PIK3R3 infiltrated well into tumours and had long-lasting cancer-killing activity."
#Immunology #immunotherapy #CARTcells

https://www.nature.com/articles/d41586-024-00305-3

CAR T cells target senescent cells, improve healthspan in mice
https://www.news-medical.net/news/20240202/CAR-T-cells-target-senescent-cells-improve-healthspan-in-mice.aspx

#CARTCells
#Senescence
#Healthspan

'The present study illustrates great potentials of chimeric antigen receptor (CAR-T) cells targeting B cell maturation antigen in treating anti-signal recognition particle myopathy, with sustained depletion of autoantibodies and therapeutic efficacies beyond 18 mo.'
#immunotherapy #CARTcells

https://www.pnas.org/doi/10.1073/pnas.2315990121

"The highly migratory phenotype is mediated by a paracrine pathway from a group of self-produced inflammatory cytokines that include IL5, TNFα, IFNγ, and IL8. We exploit this finding to “lock-in” a highly migratory phenotype by developing and expressing receptors, which we call velocity receptors"
#Immunology #Immunotherapy #Preprint #CARTcells

https://www.biorxiv.org/content/10.1101/2023.12.13.571595v1

"The F.D.A. has approved six commercial CAR-T products. Cancer specialists said the treatments have saved the lives of thousands of patients with blood cancers. Even if there is a causal link between the treatments and a small risk of a new blood cancer, the regulators said on Tuesday, the benefits of the treatment outweigh the risks. That sentiment was echoed by doctors involved in cancer treatment."
#immunology #immunotherapy #CARTcells

https://www.nytimes.com/2023/11/28/health/fda-car-t-blood-cancer.html

The effects of the CTLA4 deletion were not very surprising, what's fascinating here is how it compares to the double mutants (PD1/CTLA4).

"CTLA4 disrupted CART19 cells display prolonged surface CAR expression, increased proliferation, and enhanced CART19 effector function supported by unopposed CD28 co-stimulation, which is lost in CART19 cells deficient for both PD-1 and CTLA4"

#Immunology #Immunotherapy #CheckpointInhibitor #CTLA4 #CARTcells

https://www.cell.com/immunity/fulltext/S1074-7613(23)00407-7#secsectitle0075

"Further, when CART cells were treated with IL-4, they developed signs of exhaustion, but when CART cells were treated with an IL-4 monoclonal antibody, they showed improved antitumor efficacy and reduced signs of exhaustion in preclinical models."

#immunology #immunotherapy #CARTCells #Preprint

https://www.biorxiv.org/content/10.1101/2023.09.28.560046v1

"Although marketed CAR-T therapies have shown transformative efficacy for certain blood cancers, widespread adoption, as well as applicability to solid tumours and autoimmune indications, have been limited by safety, efficacy and operational hurdles. These hurdles include high rates of adverse events such as cytokine release syndrome (CRS), inability to overcome the immunosuppressive microenvironment typically found in solid tumours, and antigen escape and cell exhaustion that reduce durability."

#CARTCells #Immunotherapy #Immunology

https://www.nature.com/articles/d41573-023-00140-7