It turns out that ARHGAP45 also encodes the first identified minor histocompatibility antigen (HA-1) and we present a new cell therapeutic approach to target HA-1 and upregulate ARHGAP45 derived epitopes. Thanks to @LLSusa, @theNCI, @MSKCancerCenter for their support.

Excited to announce a new paper in ‪@aacrjournals.bsky.social‬ with Junwei Shi and Tony Daniyan. We perform screens of GAPs and GEFs in AML and discover a hematopoietic-specific GAP (ARHGAP45) required in a variety of hematologic malignancies:
aacrjournals.org/cancerdiscov...

Now online in Cancer Discovery @aacrjournals.bsky.social: Systematic Evaluation of GAPs & GEFs Identifies a Targetable Dependency for Hematopoietic Malignancies - by Pu Zhang, Zhendong Cao, Anthony Daniyan, Omar Abdel-Wahab, Junwei Shi, et al. doi.org/10.1158/2159...

Excited to announce our annual New York City Edward P. Evans MDS Centers Symposium across @mskcancercenter.bsky.socia & @columbiacancer.bsky.social. This year to be held at @mskcancercenter.bsky.socia. See this flyer below and register here:
forms.fillout.com/t/1wX3dGmym4us

Thanks @raflynn5.bsky.social ! congrats on the cell surface NPM1 paper this week as well.

We are excited to develop this as a novel cell therapy for myeloid leukemia patients with mutations in splicing factors. Thank you to @break-cancer.bsky.social, ASH, LLS, Edward P. Evans MDS Foundation, NCI, NHLBI, and @parkerici.bsky.social for support.

Importantly we were able to identify neoantigen-specific CD8 T cells in patients with active MDS and AML. However, these neoantigen specific T cells had clear evidence of dysfunction, likely explaining the initiation/maintenance of these malignancies.

We now find that MDS and AML patients with mutations in the splicing machinery create endogenous mis-splicing derived immunogenic peptides which are shared across patients (“public”) and were used to isolate tumor-selective TCRs.

In 2021 in collaboration with the Bradley lab we identified that pharmacologic modulation of splicing creates bona fide RNA mis-splicing derived neoantigens which can augment immune checkpoint blockade efficacy in syngeneic solid tumor models:

Mutations in genes encoding RNA splicing factors occur in 50-80% of patients with myelodysplastic neoplasms and create stereotyped changes in RNA splicing consistent across patients.

This is part of a long-standing collaboration with Rob Bradley’s lab
‪@fredhutch.bsky.social‬ and with amazing TCR discovery expertise from Chris Klebanoff’s lab @klebanofflab.bsky.social @mskcancercenter.bsky.social‬‬. Also incredible help from Jeff Molldrem @mdanderson.bsky.social‬‬‬‬‬

Excited to announce a new paper out today in @cp-cell.bsky.social discovering RNA mis-splicing derived neoantigens & their cognate T cell receptors (TCRs) as well as characterization of endogenous neoantigen T cells in leukemia patients.

authors.elsevier.com/sd/article/S...

Thanks so much @mikemfernandez.bsky.social ! Congrats on all of your success at #ASH24 and your award!