Patompon Wongtrakoongate retweeted
This is a beautiful way to visualize the pathophysiology.
B cells at different stages of differentiation occupy different compartments, express different surface markers, and drive different pathologies.
Based on this biology, it'd make sense that (for example) lupus would respond best to anti-CD19 therapies, while Sjögren’s would respond best to anti-BCMA -- though how that shakes out in trials isn't fully known.
Next-generation immune cell engagers for B cell depletion in autoimmune diseases
nature.com/articles/s41573-0…
rdcu.be/NecnUNkptUFa
This Review discusses the principles guiding the design of immune cell engagers and emerging stratgeies to improve safety and durability of response
Patompon Wongtrakoongate retweeted
Breaking
lifespan.com/blogs/magazine/…
Variants in genes involved in the production of extracellular matrix molecules could have enabled the skeletal adaptations that distinguish humans from other great apes
go.nature.com/4hoky1J
Patompon Wongtrakoongate retweeted
75% through the year, 44 new drugs have been approved.
- 18 novel mechanisms.
- 20 differentiated follow-ons.
- 6 me-too’s.
Patompon Wongtrakoongate retweeted
Smaller public biotechs, with more specialist investors, tend to generate outsized returns.
Which begs the question: which of today’s small biotechs have the most specialist investors?
Using the full landscape of all 149 specialists, here’s the top 20.
The full analysis and methods are here: breakingground.substack.com/…
Patompon Wongtrakoongate retweeted
New! Online now: Microbial aldehyde-alcohol dehydrogenase degrades metformin to limit therapeutic response in type 2 diabetes dlvr.it/TVhqcp
Patompon Wongtrakoongate retweeted
Old hearts age backwards: transplanted organs adjust to host's biological age
nature.com/articles/d41586-0…
Patompon Wongtrakoongate retweeted
An impressive study that emphasizes the role of systemic environment in the aging process an contradicts prior parabiosis work
Hearts from young donors age rapidly in the bodies of older recipients, and older hearts are rejuvenated inside young people
go.nature.com/4rzzsHf
Patompon Wongtrakoongate retweeted
Anti-CD19-engineered exosomes enable B cell-targeted anti-BAFF mRNA delivery to alleviate lupus progression dlvr.it/TVhSMY #genetherapy #celltherapy
Patompon Wongtrakoongate retweeted
Personalized neoantigen vaccines have already been shown to improve outcomes for refractory malignant melanoma and in pilot studies of pancreatic cancer, glioblastoma, renal cell carcinoma and triple negative breast cancer. But they require a tumor biopsy to identify the antigens. A new study shows it's possible to get this from a blood sample.
aacrjournals.org/cancerdisco…
Patompon Wongtrakoongate retweeted
"We stabilized mRNA vaccines ....Moderna ...and Pfizer-BioNTech ....compositions into solid-state formulations that retained 100% bioactivity after storage at 37 °C for more than 2 months."
That sounds almost too good to be true.
#science
#immunology
nature.com/articles/s41587-0…
Patompon Wongtrakoongate retweeted
ひとつのmRNAは、ゲノムの一箇所から作られる。この前提が崩れたかもしれない。
ハーバード大のグループが、逆転写酵素を使わない直接RNAシーケンシングでマウスのマクロファージを調べたところ、別々の遺伝子の配列がつながった「キメラmRNA」が3万種以上見つかった。その約88%は、異なる染色体どうしの組み合わせ。
炎症が起きると、離れた染色体上の遺伝子が核の中で引き寄せられ、そこでRNAが正確な一点で連結される。この接近はゲノムの折りたたみを担うCTCFに依存していた。
なかでもGsdmdとTmem106aが融合したmRNAは、データベースに存在しない新しいタンパク質をコードしていた。細胞膜であらかじめ待機し、炎症性細胞死の実行役GSDMDが穴を開けるのを加速させる「先回り役」らしい。量は本家Gsdmdの1割未満だが、1割足すだけでIL-1β放出はほぼ倍に。
マウスでは、これを失うと敗血症に強くなる一方、サルモネラ感染には弱くなった。感染防御と免疫の暴走が、同じつまみの両端にぶら下がっている。
がん細胞の異常として語られてきた融合遺伝子が、健康な細胞の正常な仕組みとしても存在する。狙える創薬標的の地図には、まだ空白がありそう。
nature.com/articles/s41586-0…
Patompon Wongtrakoongate retweeted
Antigen-specific regulatory T cells eliminate cognate CD4 effector T cells through perforin, granzyme B, and Bim dlvr.it/TVhcHd
Patompon Wongtrakoongate retweeted
Lipid nanoparticles optimized for large RNA cargo and tissue targeting enhance in vivo genome editing nature.com/articles/s41587-0…
Hearts from young donors age rapidly in the bodies of older recipients, and older hearts are rejuvenated inside young people
go.nature.com/4rzzsHf
Patompon Wongtrakoongate retweeted
Here come the nanoparticles to help treat cancer or get rid of senescent cells, reduce fibrosis
@ScienceMagazine @ScienceVisuals
science.org/doi/10.1126/scie…
science.org/doi/10.1126/scie…
Patompon Wongtrakoongate retweeted
In vitro induction of human germinal center B cells
science.org/doi/10.1126/scii… @SciImmunology 🇯🇵
Patompon Wongtrakoongate retweeted
She lived to 117 — the oldest verified age ever recorded — and her body told two completely different stories at once.
Maria Branyas had the telltale signs of extreme aging: razor-thin telomeres and an inflamed immune system. But she also carried something rare: low inflammation, a gut brimming with beneficial bacteria, and cells that were biologically younger than her 117 years.
Because she never developed a major disease, researchers led by Dr. Manel Esteller at the @CarrerasIJC (Josep Carreras Leukaemia Research Institute) could finally study aging on its own, without illness clouding the picture — the most detailed biological deep-dive ever done on a supercentenarian.
Their conclusion, published in Cell Reports Medicine: extreme longevity might not mean dodging aging altogether, but surviving it while holding onto the right protective traits.
Curious what those traits were?
Read the full study here: sciencedaily.com/releases/20…
#Longevity #AgingResearch #Geroscience #Epigenetics
Patompon Wongtrakoongate retweeted
腫瘍免疫にT細胞受容体の特異性ってそこまで重要じゃないの?👀読まなきゃ...
9/8のNature Immunology
Intratumoral T cell activation kills tumors regardless of T cell specificity
nature.com/articles/s41590-0…




























