Evan Weber
@EvanWeberPhD
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Assistant Professor @PennMedicine @ChildrensPhila | @parkerici | CAR T cells, immunotherapy, epigenomics, T cell exhaustion | he/him
Philadelphia, PA
Joined June 2018
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Pinned Tweet
Memory genes are enriched in CAR T cells that persist and control tumors in patients. But which transcription factors drive beneficial memory programs?
We answer this in our lab’s first paper in
@Nature
led by
@alexdoan96
@kpmueller1
@andy_yhchen
. 1/
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I am thrilled to share our new paper out in
@ScienceMagazine
! We show that transient disruption of CAR signaling, or "rest", can reinvigorate exhausted CAR-T cells and boost anti-tumor functionality
#CART
#immunotherapy
#IO
Thread 1/
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A truly brilliant study and candidate for paper of the year.
Authors developed a universal system to detect cell-cell interactions in vivo. In one example, they use it to discover non-canonical CD8 priming events by monocytes during acute infection.
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FISHnCHIPs is the greatest science acronym of all time. I’ll die on this hill.
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🚨 Big announcement 🚨
The Weber Lab will be opening its doors in February 2022
@CHOP_Research
@PennMedicine
!
I'm building a multidisciplinary team to help cure kids with cancer. Please email weberew
@chop
.edu or visit for more info.
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Last day in the
@MackallLab
@StanfordMed
😢✌🏻. What a ride it has been. So grateful for the mentorship, friends, and memories.
Now on to my next adventure
@ChildrensPhila
@PennMedicine
!
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We've known for years that CD27 expression on manufactured CAR T cells correlates with clinical responses. Elegant work from the Riddell lab shows there's more to the story.
Ligating CD27 during CAR T manufacturing induces memory genes and boosts potency.
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I mean...
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Why would one intentionally induce T cell exhaustion? To prevent autoimmunity, of course! What a cool idea and paper.
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Colleagues, please retweet!
I’m recruiting postdocs for my new group
@ChildrensPhila
and
@PennMedicine
who are interested in developing and translating novel approaches to enhance CAR-T cell therapies. Apply below or send your CV to weberew
@chop
.edu
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In the
@MackallLab
, we often debated about the best predictive biomarkers for good CAR-T cells. IL-2 secretion was almost always at the top of the list. This paper has me wondering if we were onto something!
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Lab update: we successfully made our first batch of CAR-T cells! Now we’re cookin’
#proudPI
@joseaumana
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Lab update…
I’m ecstatic to welcome Kat Mueller (
@kpmueller1
) to my lab for her postdoc! Upon finishing her PhD with
@sahakris
, she will bring considerable expertise in gene editing, CAR-T, scRNA-seq, and much more. Can’t wait to see what she accomplishes!
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After some early troubleshooting, my lab’s very first rotation student
@joseaumana
got some great data last week and is on his way to becoming a cloning master. Love it! 💪🏻💪🏻💪🏻
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Finally, a case report! Dasatinib appears to have reduced CRS and ICANS in a patient treated with CAR T cells (Tisagenlecleucel) who was refractory to IL-6 blockade and steroids. The patient exhibited a complete response and is 2 years out from therapy.
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🚨We are hiring a Research Assistant to help us supercharge CAR T cells!
Candidates of all experience levels are encouraged to apply. Some lab experience is required, mouse experience is preferred. 2-year minimum commitment.
Please retweet!
Apply here:
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Two exciting studies out in
@Nature
show that high tumor PGE2 limits IL-2 sensing and antitumor function in TIL. Disrupting this axis can potently enhance antitumor responses. Nice work
@CoukosGeorge
@JBoettcherLab
and teams!
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WOW, thank you to
@sitcancer
for this incredible honor, Dr. Rosenberg for his foundational contributions to cancer immunotherapy, my phenomenal mentor
@cm35c
, and my supportive colleagues. 🙏🏻
#SITC21
Congratulations to
@EvanWeberPhD
, recipient of the 2021 Steven A. Rosenberg, MD, PhD, Scholars Award!
#SITC21
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Interesting study on the origins of one of our favorite topics, tonic CAR signaling
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Fantastic and comprehensive review on emerging mechanisms of T cell dysfunction in cancer and strategies to overcome them by
@CaitlinZebley
@Zehn_Lab
@Kyttaro_Therapy
@hongbo_chi
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Happy to report that the first ever joint Weber Lab/
@LeyuanM
Lab CAR club meeting was a success! We discussed the recent Nature paper from
@MarcelaMaus
’s group, which raises some interesting and important questions around tailoring CAR-T cell therapies for liquid vs solid tumors.
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BATF knockout in CAR-T cells reduces exhaustion and enhances antitumor activity
Interesting findings, and contradictory to those published last year by Patrick Hogan's group in which ectopic BATF enhanced CAR-T cells. A+ on the graphical abstract! 😁
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Wonderful study from
@MSubklewe
and team which further demonstrates that intermittent (rather than continuous) CAR T activity can stave off exhaustion and boost potency. Less is more!
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An absolute GAME CHANGER for CAR T...the first legitimate AND gate and a paradigm shift in T cell proximal signaling dogma.
So happy that
@Majzner_Lab
ignored me when I said it would be impossible for a T cell to signal independently of Lck 😂
Happy to share the newest paper from our lab. Led by technician extraordinaire Aidan Tousley (soon to be an MD/PHD student!), this manuscript details our attempts to reimagine the structure of CARs to improve their specificity and efficacy.
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The first lab happy hour with our entire team was a success 😁🍻. Thankful for the opportunity to mentor these bright, motivated scientists.
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Very excited to share the preprint version of our manuscript!
We show that transient disruption of CAR signaling (i.e. "rest") via CAR downregulation or inhibition of Src kinases can reverse CAR-T cell exhaustion and augment functionality
#CART
#TCellExhaustion
#Immunotherapy
Transient "rest" induces functional reinvigoration and epigenetic remodeling in exhausted CAR-T cells
#bioRxiv
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First ever lab party! So many things to celebrate, including a farewell to our med school-bound technician. Very fortunate to work with such wonderful people 🙂
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Crystal Mackall
@cm35c
@MackallLab
receiving the
@sitcancer
Smalley award, then schooling us on the history of cancer immunotherapy and showing us a path forward for using CAR-T cells against solid tumors. Fortunate to play a small part in the effort. Congrats Crystal!
#SITC2021
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Ever wonder what endothelial cell Ca2+ signaling looks like when a leukocyte squeezes out of a blood vessel? Right before I finished grad school
@NUFeinbergMed
, we developed an intravital imaging model to do this. 👇
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Today is our lab’s 1-year anniversary! Time has flow by, but we’ve come such a long way since last Feb thanks to the incredible trainees who make our work possible.
Shoutout AI Drake for writing a song celebrating this momentous occasion
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A nice review on the current state of TIL therapy
The first tumour-infiltrating lymphocyte (TIL) therapy for cancer could be approved by the FDA early next year, and a diverse pipeline of other TIL candidates is in development - find out more in our latest news article
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Pleased to share our review article in
@CellCellPress
on the past, present, and future of immune cell therapies! Big thanks to co-authors
@cm35c
@MarcelaMaus
,
@StanfordMed
@StanfordCancer
@MGHCancerCenter
@harvardmed
#CART
#CARTCell
#CARNK
#immunotherapy
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One of my favorite things about training under Crystal is that she possesses a “go for it” attitude that makes any crazy idea seem feasible, but also a pragmatic side that lends itself to rapid clinical translation. A perfect recipe, IMO
Very well deserved, congrats
@cm35c
!
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Quick thoughts on being a
#NewPI
for all of 2 weeks (thread):
It’s been absolutely exhilarating, but also jarring. Like, I have an office for the first time in my career (🤯) and an entire lab for which I’m responsible. Even my interactions with colleagues feels different. 1/3
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What are some common (or uncommon) traps that junior PIs fall into?
2.5 yrs into this job and I'm still learning from my mistakes...I made the short-sighted decision to schedule a vacation right before a grant deadline ☠️.
NEVER AGAIN
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Game-changing work from
@yarmo111
and the Maris lab
@CHOP_Research
showing that specific peptide/HLA combos are enriched in neuroblastoma and that they can be targeted with conventional scFv CARs!
Are peptide-centric CARs the future of CAR-T therapy?
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A very special day indeed…our first Weber Lab meeting! Great data and lively discussion, and I couldn’t be happier about it. Big thanks to
@alexdoan96
for presenting
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🚨 New Mackall lab study out in
@NatureMedicine
! 🚨
Johanna Theruvath et al. show that intraventricular injection of B7H3-targeting CAR T cells leads to enhanced kinetics and potency in an aggressive pediatric brain tumor model (ATRT).
#CART
#CARTcell
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It's finally out! Tremendous effort from lead author Rachel Lynn,
@cm35c
@molecular_elena
@GoodZinaida
@hima_anbunathan
our collaborators
@HowardYChang
@Satpathology
@michelle_monje
and the many co-authors not listed here.
#CARTCells
#tcellexhaustion
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Pretty sure that “Not angry, just disappointed” is a TCF7+ Tpex
It's like a jungle sometimes it makes me wonder
How I keep from going under
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Kiss of death 😘
Small but mighty! This is a video of a killer T cell of the immune system destroying a monstrous ovarian cancer cell. I recently captured this data on a spinning disc confocal microscope.
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Still buzzing from
@alexdoan96
and
@kpmueller1
presentations at
#SITC2023
. Couldn’t be prouder of these rockstar trainees 💪🏻💪🏻
See you next year
@sitcancer
!
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Love this new review from
@drnickrestifo
and Luca Gattinoni on engineering synthetic T cell states for T cell based immunotherapies.
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LOVE waking up and seeing the scientific community so galvanized and unanimously psyched about the Nobel announcement and the deserving awardees🧑🏻🔬🧬🔬
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First grant submission as a
#NewPI
is in the books! Please tell me this gets easier over the time, lol.
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I never thought I’d see my toddler approach me with a pretend COVID swab (i.e. a pen) while gently whispering, “this will just take a second”
…but here we are
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Matthew Porteus easily wins the "Best Title" award at
#KSgenome
#KScelltherapy
😂
(not to mention the incredible work coming out of his lab)
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Lovely study by
@GreenLymphoLab
and Qing Deng in which they performed scRNA-seq on 59 (!!!) CD19 CAR T cell infusion products...and the data is publicly available. A logical follow-up to their highly-cited 2020 Nat Med paper.
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Impressive study demonstrating that CD62L+ Tpex are the "true" stem-like exhausted subset that respond to anti-PD-1
A bit counterintuitive, since CD62L is super sensitive to activation state and downregulates after TCR signaling. I wonder how/why it's maintained in this setting!
New out in
@Nature
: Together with
@KalliesLab
my lab
@TU_Muenchen
identified the key stem-like CD8 T cell subset and its signature transcription factor responsible for maintenance of exhausted T cell immunity and responsiveness to checkpoint blockade!
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CONGRATS to my brilliant mentee
@alexdoan96
for receiving a
@sitcancer
Young Investigator Award! He'll be giving a short talk on memory reprogramming in CAR T cells at the annual meeting in November. Can't wait!
With a record-breaking 1,500+ abstract submissions, uncover the latest breakthroughs in immunotherapy with the cutting-edge science from Regular and Young Investigator Award abstracts at SITC 2023. Browse Abstract Titles & Authors:
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Our SUIP summer intern, Cynthia Schneider, did a fabulous job today presenting her project at the
@IDEAL_Research
poster session! Very proud of her and her mentor
@kpmueller1
😁
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Exciting results from
@StanfordMed
showing >50% CR in adult patients treated with CD22 CAR T who previously relapsed after CD19 CAR T therapy. Importantly, "of the 20 patients with a complete response after receiving CAR22, only three (15%) patients relapsed"
Excited to see our article in Lancet today!
Grateful to have been part of an amazing team studying CD22-directed CAR T-cell therapy for DLBCL progressing after CD19-directed CAR T-cell therapy.
@StanfordCancer
@StanfordMed
@LymphCo
@EHA_Hematology
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Truly honored to be included in this group of scientists. Congrats to the other awardees, and a BIG thank you to
@parkerici
for their support!
#immunotherapy
#CART
🧑🔬🧬🧪
They are rising star researchers with ideas that can change cancer care as we know it. Congratulations to PICI’s 2021 class of early career research awardees!
#CancerFearsPICI
@BeltraJC
@Themis_Brown
@EvanWeberPhD
@CalebLareau
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Doing very important* science** things today in the Weber lab
*annoying
**maintenance
@joseaumana
@kpmueller1
@G_Rouin
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An extremely fun day chatting with the students and faculty
@SanRaffaeleMI
. Thanks to Monica Casucci for the opportunity to visit!
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Brilliant work from my friends
@Dori_Na_Krzemie
@molecular_elena
in the
@MackallLab
demonstrating how metabolic reprogramming and enhanced stemness can boost CAR T function. Congrats!
Our latest work out in Cancer Cell.
#CART
#immunometabolism
#immunosuppression
Inosine induces stemness features in CAR-T cells and enhances potency
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Great to reconnect with friends and colleagues
@parkerici
retreat, not to mention the spectacular and inspiring scientific talks!
@CalebLareau
@LouaiLabanieh
@C_Alanio
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Really cool work from the Fraietta Lab
@PennMedicine
demonstrating that dual knockout of 2 key transcription factors can enhance the activity of human CAR T cells. Lots of interesting biology in here as well!
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Psyched to share the stage with
@kean_leslie
@SchietingerLab
@GiedreKrenciute
tomorrow at
#ASH22
to discuss advances in mitigating CAR T cell exhaustion and present some unpublished work…hope to see you there!
#ASH22
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Thank you
@TheScientistLLC
and
@aparnanathan
for featuring our work! (and shoutout
@KlebanoffLab
for taking the time to provide some nice commentary and perspective)
CAR T cells are hard workers, but even they face burnout.
New research from
@evanweberphd
at
@PennMedicine
showed how one transcription factor can make CAR T cells more resilient to exhaustion and better cancer fighters.
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It’s amazing to me how insights gleaned from Coley’s Toxins are still applicable today in cancer immunotherapy. Super interesting paper.
New in
@Nature
: bacteria derived peptides are presented on HLA in glioblastoma and TILs recognize these peptides
implications for vaccine and microbiome-based therapeutics for GBM in the future
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I can only assume
@Majzner_Lab
knocked it out of the park at
#AACR2022
. Congrats to the entire
@Stanford_CCT
team for helping advance CAR-T for solid tumors!
@MackallLab
I can’t remember the last time an ovation was given right in the middle of a talk while data were being presented. Congratulations on this step forward for a terrible disease
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Incredible effort by
@Heitzeneder_S
et al to engineer a ready-for-clinic CAR against solid tumors that is safe and highly potent in multiple cell line and PDX tumor models
#CART
Excited to share our new manuscript in Cancer Cell detailing how CAR engineering can lower the antigen density threshold approximately 10-fold. Critical insights for targeting many clean antigens expressed at "lower levels".
#CARsforKIDs
. .
#GPC2CARs
.
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CD8+ T cells in the cancer-immunity cycle: CD8+ T cells are “end effectors” of cancer immunity. Wherry, Kaech, Giles, & Globig review the current understanding of CD8+ T cell differentiation and function in cancer, discussing recent advances within a four-signal framework that
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An important step in making CAR T accessible to more patients
Revamped
#manufacturing
! Self-sustained
#India
leading from the front on CAR-T
#innovation
. Single treatment of
#NexCAR19
, manuf. by
#Mumbai
's
@ActImmuno
, costs $30-40K. Commercial CAR-T therapies cost b/w $370-$530K, excluding hospital fees etc.
@Nature
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Hot off the press from the Mackall lab!
Robbie Majzner shows us that slight alterations to the CAR architecture can raise or lower the antigen density requirement for
#CART
cell activation. Major implications for the future of CAR design!
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Fun session and roundtable at
#iwCART23
on overcoming limitations to CAR T. Lots of encouraging new preclinical and clinical data…the future is bright for cell therapies!
We just had a fantastic roundtable discussion on Current Challenges in CAR-T!
#iwCART23
#iwCART
#CART
#CellularTherapies
@VJOncology
@VJHemOnc
@MarcoLDavila
@FilipIonescu5
@GreenLymphoLab
@EvanWeberPhD
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Psyched to be back in DC for the
@ASGCTherapy
annual meeting! Looking forward to great science and conversation 🧑🔬🧬
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Excited to moderate today's
@theNCI
Cancer Moonshot Seminar at 12pm EST on immunotherapies for adult and pediatric cancer featuring Kris Bosse from
@CHOP_Research
and
@XiaoHuangNano
from
@drexelbiomed
.
Register here!
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Despite having higher “academic abilities”, ex-postdocs “forfeited 17–21% of their present value of income over the first 15 years of their careers.”
A lot of worrisome stuff in here. The status quo is unacceptable.
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WOW 😮. mRNA vaccines for cancer are safe, feasible, and likely efficacious. Incredible findings by
@TheVinodLab
and team.
1. ENTER
#mRNAvaccines
for
#pancreaticcancer
! Long-term
#PDAC
survivor story PART3.
"Do
#PDACs
REALLY have vaccine neoantigens (NAs)"? (aren’t they lowly mutated?)
If each patient = own NAs, how do you vaccinate?
Maybe mRNA? But how?
@Nature
👇🏽 [1/32]
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Love this idea. The external pressures to move quickly in lab make it easy to forget that we are scholars and should therefore be doing scholarly things (like reading and deep thinking).
Our lab is taking a week ‘off’ for reading, writing, and thinking. It’s an experiment, but one I hope works. I think the pace of science has become too fast and there’s not enough time to just sit with your theories/data and allow your ideas to mature.
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“Cluster 9 is particularly interesting because…”
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We all know the feeling, lol
Honestly being a PhD student at a conference can feel like this sometimes
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The story behind the story! Collaboration and team science for the win.
I'm wildly proud to share our FIRST Weber Lab paper, out today in
@Nature
! I want to share a story about how this whirlwind of a project came together. A 🧵 on teamwork, open science, and how far we can go when we intentionally build a culture of trust in research. 1/
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Psyched to hear some amazing science and catch up with friends at
#SITC2023
For those attending, our unpublished work will be presented at Poster 247 and
@alexdoan96
’s talk in the cell therapies plenary on Sunday!
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Honored to have played a small part in this study lead by
@lamarchecaroli1
and
@mklevings
describing CAR Treg exhaustion!
Tonic-signaling CARs can induce exhaustion in Tregs ! Here are our results if you want to learn about the phenotype, transcriptome, metabolism and epigenetism of those cells.
@mklevings
@PNASNews
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Couldn’t have picked a better day for my first Sixers game. Great crowd and clutch win!
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Very cool study that further implicates T cell stemness as a major therapeutic axis for T cell immunotherapies.
Congrats
@GuillermoORang1
@Chrystal_Paulos
and the team!
Progressively enhancing stemness of adoptively transferred T cells with PI3Kδ blockade improves metabolism and anti-tumor immunity
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I’m not saying I’m becoming a Philly sports fan, but I’m not NOT saying I’m becoming a Philly sports fan… 🦅
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Hey look, CAR T maestro
@JoeFraietta
is now on Twitter/X! Give him a follow 👇🏻
Happy New Year 2024! Let's embark on a year of shared wisdom and collective exploration!
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Absolutely love this, but I imagine CAR-T working more like 👇🏻
I'm working on bringing some of my previous scientific illustrations to life as animations. Short animation stylizing the idea of CAR T-cell therapy; here, engineered T-cells conducting surveillance, searching for cancer cells to destroy.
#sciart
#Blender3d
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I think about T cells a lot, but much of this is new to me! Thanks
@kischober
for this important thread and reminding us of how we got to where we are today.
On my way to
@badw_muenchen
, and as often then finding time and inspiration to read stuff that I should know, but actually don’t. Here’s a short history of the discovery of the T cell receptor. 🧵
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If you’re going to read a paper today, make sure it’s this one from the ultra-talented
@LouaiLabanieh
!
Easily one of my favorite projects (and people) from the
@MackallLab
. Major implications for the future of CAR design. 👇🏻
Thrilled to announce that our SNIP paper is live
@CellCellPress
! SNIP is a high-performance drug-regulated CAR platform that is optimized for the clinic--plans for a trial are already underway
@StanfordMed
.
#CART
#Immunotherapy
#SynBio
#Cancer
.
1/
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Wow! Mutations in the extracellular domain of BCMA didn’t affect BCMA surface expression but prevented anti-BCMA CAR binding, leading to relapse after BCMA CAR T therapy.
Very excited to share our work
@NatureMedicine
() on resistance mechanisms to CART and T cell engagers in MM! A big thank you to my amazing mentors
@nbahlis
and Paola Neri, collaborators
@FrancescoMaura4
,
@RascheLeo
,
@PedalheadPHX
and all co-authors!
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A terrible tragedy, and another unfortunate result of the absolutely batshit crazy driving culture that is tolerated in Philly.
@PhillyMayor
must do more to make drivers, bikers, and pedestrians safer in our city.
The cyclist struck and killed while riding near Rittenhouse Square last night has been identified by family as Barbara Friedes, a doctor at the Children's Hospital of Philadelphia.
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🚨Attention colleagues (esp. in Chicago)! If CAR T is your jam, please consider registering for the
@UChicago
Jonas Center Cellular Therapy Symposium on September 22nd. Looking forward to sharing some unpublished data and chatting with other attendees.
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