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EHA 2025 | What makes mutant CALR an attractive therapeutic target in MPNs?
In this video, Lucia Masarova, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, comments on the potential of mutant calreticulin (CALR) as a therapeutic target in myeloproliferative neoplasms (MPNs), noting that its presence on the surface of cancer cells makes it accessible to immunologic approaches. This interview took place at the 30th Congress of the European Hematology Association (EHA) in Milan, Italy.
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Transcript
It’s just a different driver of the disease where calreticulin again binds on the surface. So a JAK2 mutation remains inside the cells and MPL works for the thromboreceptor. So calreticulin, it’s probably the first novel exciting discovery where these mutant calreticulins travel on the cell surface and that’s why they’re open to immunologic address and approach...
It’s just a different driver of the disease where calreticulin again binds on the surface. So a JAK2 mutation remains inside the cells and MPL works for the thromboreceptor. So calreticulin, it’s probably the first novel exciting discovery where these mutant calreticulins travel on the cell surface and that’s why they’re open to immunologic address and approach. So it’s easier to develop antibodies and then hopefully with that to attack them and basically attach to the calreticulin mutation and then get rid of them. That’s a similar principle we have across hematology or even solid tumors where we know that cancer cells express certain mutant proteins or different markers where we are able to develop drugs. Either it’s a simple antibody or it’s an antibody that’s armored or it’s an antibody that engages the immune system or even the chimeric antibodies that we have approval across hematology and almost every single cancer but nothing in MPNs. So this is a first opportunity first in a human and proof of concept approach where we will be able to go in the target which is specific for the cancer mutations and calreticulins for these people are mutants so they’re only in cancer cells.
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