Blake Smith

It’s hard not to get addicted to this. From side conversations with @MEBirnbaum to an incredible result for patients. So proud of the Kelonia team for all the hard work it took to make this real.

The first patient with multiple myeloma has been dosed in the inMMyCAR study, our first in-human Ph 1 clinical trial of our in vivo gene therapy, KLN-1010. Learn more about the inMMyCAR clinical trial and our unique gene delivery platform: keloniatx.com/kelonia-therap…

Check out @Steph_Gaglione's amazing preprint introducing a highly scalable (and inexpensive) approach to TCR synthesis that enables library-on-library screening of TCRs + antigens 👇!

@dylanvneel @harvardneuromds @MGHNeuroSci @BWHNeurology congrats Dylan! this is such great news 👏

Beyond excited to have matched @harvardneuromds ! Can’t wait to meet my co-residents, learn some cool neurology and hopefully help a lot of patients! #Neurology #Match2025 @MGHNeuroSci @BWHNeurology

here's a peek of Dr. Perez showing this work - how diverse CAR libraries (inputs) can be leveraged to generate useful datasets that describe differential CAR phenotypes (outputs) at his thesis defense yesterday 👇 super lucky to be your lab mate & play a small part in this work!

An incredibly impressive body of work from the newly-minted PhD @calebrperez comparing clinical candidate CAR-T architectures head-to-head at single cell resolution, shedding light on mechanisms of differential CAR-T efficacy in vivo with insights into better construct design 🚗

In sum, Dezfulian et al. have successfully re-centaured T cell antigen discovery around CD4+ T cells 😉 cell.com/cell-reports-m…

The authors then applied their TScan-II methodology to uncover antigens in cancer, autoimmunity, & infectious disease across many different MHC class II alleles & TCRs Their screens uncovered antigens recognized by clonally-expanded CD4+ T cells from Sjögren's syndrome patients

For their last trick🪄, the authors introduced the candidate human TCR antigen-binding variable region atop a murine TCR constant region resulting in a human-mouse hybrid TCR that reduces cross-reactivity with the endogenous TCR They termed these chimeras "centaur T cells"🏃🐎

For the T cell side of the equation, they made use of the granule-releasing properties of primary CD8+ T cells, but introduced a CD4 co-receptor alongside a candidate T cell receptor (TCR) of interest But what if the introduced TCR mispairs with the endogenous CD8+ T cell's TCR?

Wrote a Spotlight piece together w/ lab mate @amandaochan & @MEBirnbaum covering an impressive new methodology from @elledge_stephen's group that enables MHC class II antigen discovery for CD4+ T cells called TScan-II cell.com/cell-reports-m…

They also needed to introduce a reporter of T cell antigen recognition The reporter is an infrared fluorescent protein (IFP) that only becomes fluorescent upon exposure to cytotoxic granzyme B (GzB), representing a functional & sortable readout of cognate CD4+ T cell recognition

But to do so, the authors needed to engineer both the antigen presenting cells (APCs), alongside the primary T cells used For the APCs, they modified HEK-293 cells (eHEK-293-II) to lack MHC class I, but present MHC class II allele(s) of interest alongside appropriate machinery

TScan-II allows for genome-scale interrogation of MHC class II antigens using endogenous processing & presentation machinery of antigen libraries, alongside physiological T cell activation & degranulation (GzB) 👇 pubmed.ncbi.nlm.nih.gov/38016469/

new @runthelistpod episode is now out hosted on @MHMedical's AccessMedicine webpage! best part about it? you can search for key words & phrases to more easily listen to high-yield content 🤯 accessmedicine.mhmedical.com/MultimediaPlay…

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 nature.com/articles/s4158… 👇🏽 [1/32]

@blhorton ncbi.nlm.nih.gov/pmc/articles/P… happy to put you in touch with the first author too if you want!

Hey sci twitter - does anyone know a human study with single cell RNA + TCR seq of matched blood and tumor? Would be ideal if it had checkpoint blockade but that’s a big ask…

So excited to be at #SITC22 in Boston hearing from some of the giants in the field!

@leah_pierson 🔥

I've been doing weekly "accountability check-ins" with other grad students who are also writing their dissertations, and we have finally perfected the format: 1) go to a brewery 2) complain for two hours 3) leave 4) post goals in the group chat

@ESmithMDPhD @DanaFarber this is so incredibly exciting, congrats to you @ESmithMDPhD & your team! such an amazing turnaround from the 2019 publication to now 👏

Next Steps: A multicenter trial of a similar GPRC5D product (NCT04674813). BCMA/GPRC5D dual-targeting (aacrjournals.org/bloodcancerdis…; NCT05431608) trial. In the lab @DanaFarber we are working on novel approaches for gene/cell/mRNA immunotx of MM & solid tumors. 10/10

Our report of first-in-human GPRC5D-targeted CAR T cells for MM is out in NEJM! The trial was led by Sham Mailankody and could not be done without the amazing clinical, correlative science, stats, & cell manufacturing teams. Happy to share our bench>bedside journey 1/10