We are excited about the potential for anti-CD70 CAR-Ts to make a difference for high-risk #myeloma patients

Special shout-out to our Junior Specialist Sanjana Prudhvi, who designed our Visual Abstract. We are lucky to work with such an amazing team, including everyone in the Wiita Lab @ucsfcancer.bsky.social and our collaborators. (10/10)

Finally, we developed a proof-of-principle dual-targeting CAR against both BCMA and CD70 as a potential strategy to avoid antigen escape–mediated resistance in #HRMM (9/10)

We also evaluated epigenetic regulation of CD70 in #myeloma, using a machine learning model to predict and then test key transcriptional regulators of surface expression (8/10)

While all anti-CD70 CARs demonstrated clear efficacy against myeloma cell line xenograft models in vivo, the CD27-based CAR showed remarkable >80-fold expansion‼️ versus scFv-based CARs, suggesting a highly favorable phenotype for clinical translation (7/10)

We then used the crystal structure of CD70 bound to its natural receptor CD27 to develop a structure-guided, optimized CD27-based CAR to compare to standard “scFv” based CAR, using frameworks containing either CD28 or 4-1BB costim domains. (6/10)

Analysis of paired tumor RNA sequencing data from
‪@themmrf.bsky.social‬ CoMMpass study, cell surface #proteomics, and flow cytometry revealed CD70 was present on primary #myeloma. CD70 transcript was strongly enriched in high risk genotypes t(4;14), gain 1q, and loss 1p (5/10)

...Samir Parekh at Icahn Mount Sinai, Stieglitz lab and the myeloma clinical group @ucsfcancer.bsky.social . Major support from Myeloma Solutions Fund, NIH NCI, and
UCSF Living Therapeutics Initiative (4/10)

This work was co-led by myself, Adila Izgutdina, and
@bonellpatinoe.bsky.social under mentorship of @apwiita.bsky.social, + collab w/ Ben Barwick and Larry Boise @winshipcancer.emory.edu, ‪@jdlicht.bsky.social,
‪@shanmugamlab.bsky.sociall, @kortemmelab.bsky.social, and... (3/10)

In this work we show CD70 is a novel CAR target enriched in #HRMM. We used structure-guided design to optimize a CD27-based anti-CD70 CAR-T that outperforms scFv-based CAR-Ts in preclinical efficacy studies. (2/10)