Michael Jain
michaeldjain.bsky.social
Michael Jain
@michaeldjain.bsky.social
170 followers 55 following 16 posts
Lymphoma and CAR T at Moffitt Cancer Center in Tampa, Florida
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Reposted by Michael Jain
'Why we have evolved so many cytokines for so few transcriptional regulators is not entirely known, but it suggests that the diversity in cell types that can send a signal and cell types that can receive them is more important than diversity in transcriptional programs.'
Cytokines in cancer
Kureshi and Dougan discuss the roles of cytokines in the tumor microenvironment. Although there is a sophisticated understanding of cytokine networks, therapeutically targeting cytokine pathways in ca...
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Paper in Cell finds that YTHDF2 degrades CD19 and MHC II mRNA while promoting ATP synthesis in B cell malignancies. Could be a mediator of resistance to CD19-targeted therapies.
YTHDF2 promotes ATP synthesis and immune evasion in B cell malignancies
@cellcellpress.bsky.social @zhenhuachen.bsky.social
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In the second, Doris Hansen presents a matched real world analysis comparing cilta-cel to ide-cel. At Moffitt, we are mainly using cilta-cel now. 3/3
First, Ciara Freeman presents the new Arcellx/Kite BCMA CAR T data for myeloma. Looks to be the Goldilocks of CAR T - extremely effective but no cases of Parkinson’s or cranial nerve palsies to date with 150 pts treated. 2/3
Two incredibly important abstracts presented by @moffittnews.bsky.social myeloma investigators at #ASH24. 1/3
Lawrence David (Duke) presents “FoodSeq” - everything we eat is alive and has a genome. Some DNA remains undigested. By 16S seq of stool, he can see everything we have eaten, with an alpha diversity “diet diversity” score. Followed diets of transplant patients just by following stool samples! #ASH24
Controversial opinion: in lymphoma, investigators will subcategorize into many clusters and claim a biology for one of the clusters. This is fine, but it is nearly impossible to validate this data or do a clinical trial. If there are 5-10 clusters, we need 5-10x the number of patients.
Trang Vu (Ruella lab/Vittoria bio) shows that KO of CD5 in CAR T cells leads to better function by increasing JAK/STAT signaling. Clinical trial in T cell lymphoma underway. #ASH24
Sleiman (Saar Gill lab UPenn) presents an EGFR-tagged IL-2 that can only bind to their CAR T cells and not non-CAR cells. In a macaque model, saw CRS and B cell aplasia without needing lymphodepleting chemotherapy. “Cis-targeted IL-2”. #ASH24
Agree, and also, what determines their homing?
Josh Brody (Mt Sinai) shows that most lymphoma biopsies have a few CD20 negative cells (some more than others). They have a plasmablastic phenotype and may be targetable. Q - do patients who relapse after bispecifics and are CD20 neg have a more plasmablastic phenotype in their relapsed lymphoma?
David Stahl (Cologne) shows that myeloid cells in the DLBCL TME express CSFR1 and have poor patient outcomes after CAR T. Axatilimab is a GVHD drug that blocks CSFR1 and could improve outcomes. Interestingly, CSF1 ligand may be from Tregs. #ASH24
Kelvin Mo (Stanford) shows that M2 macrophages in the DLBCL TME produce CCL8/CCL13 and have a high IFN signature, associating with poor clinical outcomes after CART. At Moffitt we have a clinical trial of a JAK inhibitor that we think will reduce myeloid IFN in highly inflamed CAR T patients.
Fascinating work by Bacchisio Ziccheddu and Francesco Maura (UMiami) outlining that tumor loss of MHC I (with resultant NK inhibition) associates with relapse after CAR T in patients treated by us at Moffitt. Suggests that CAR T needs to recruit other aspects of immunity to work!
Fascinating study where they label CAR T cells and follow their trafficking in patients! Immediate biodistribution is to the liver and spleen, and they can see whether the Car goes into extramedullary masses. What explains differences between patients?
Up next, the #ASH24 #MyelomaSky **Clinical Abstracts - RRMM @ash-hematology.bsky.social
1029 CAR-T Cell Therapy in Advanced Myeloma with EMD In Vivo Imaging and Molecular Monitoring Study (CARAMEL): First Results of Cu-64 Radiolabelled Nanoparticle PET-CT and PET-MRI
ash.confex.com/ash/2024/web...
Paper: CAR-T Cell Therapy in Advanced Myeloma with Extramedullary Disease – an <em>In Vivo</Em> Imaging and Molecular Monitoring Study (CARAMEL): First Results of Cu-64 Radiolabelled Nanoparticle PET-...
ash.confex.com
One person’s immunodeficiency could be another person’s lymphoma target