ASH 2022 | The promise of mutant CALR antibodies for the treatment of MPNs
Claire Harrison, MD, FRCP, FRCPath, Guy’s and St Thomas’ NHS Foundation Trust, London, UK, comments on the mechanism of action of monoclonal antibodies targeting mutant calreticulin (mCALR), highlighting their potential in the treatment of myeloproliferative neoplasms (MPNs). Prof. Harrison mentions INCA033989, a novel mCALR-directed antibody that was shown to effectively inhibit oncogenic signaling in patient cell lines and mouse models. This interview took place at the 64th ASH Annual Meeting and Exposition congress in New Orleans, LA.
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Transcript (edited for clarity)
So, super exciting and game changing, maybe, for the MPN field. But maybe we’re a little bit jealous of the other fields where they all have a kind of antibody therapy, et cetera. At the plenary session at this year’s ASH was a presentation about the development of a new calreticulin antibody and its efficacy in-vitro.
So, just to remind viewers that mutant calreticulin is expressed on the cell surface, it’s actually secreted, as well, and it can act on normal stem cells, but it also will be secreted, binds to MPL, which is the TPO receptor and triggers JAK-STAT signaling...
So, super exciting and game changing, maybe, for the MPN field. But maybe we’re a little bit jealous of the other fields where they all have a kind of antibody therapy, et cetera. At the plenary session at this year’s ASH was a presentation about the development of a new calreticulin antibody and its efficacy in-vitro.
So, just to remind viewers that mutant calreticulin is expressed on the cell surface, it’s actually secreted, as well, and it can act on normal stem cells, but it also will be secreted, binds to MPL, which is the TPO receptor and triggers JAK-STAT signaling. So, the antibody is specifically targeted to mutant CALR, and has been shown in cell lines as well as in patient cells and a mouse model, to be able to abrogate the signaling through the MPL receptor, and potentially to control, for example, thrombocytosis or high platelet count as a marker of disease. So this is potentially a game changer in the field, and it’ll be really exciting to see this molecule being introduced into clinical studies.
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Disclosures
Geron: Membership on an entity’s Board of Directors or advisory committees; Keros: Consultancy; Constellation Pharmaceuticals, Inc., a MorphoSys Company: Membership on an entity’s Board of Directors or advisory committees, Research Funding; EHA: Other: Leadership role; MPN voice: Other: Leadership role; AbbVie: Membership on an entity’s Board of Directors or advisory committees; Incyte: Speakers Bureau; Shire: Membership on an entity’s Board of Directors or advisory committees; Sierra: Honoraria; AOP Pharma: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Promedior: Membership on an entity’s Board of Directors or advisory committees; Roche: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Gilead: Membership on an entity’s Board of Directors or advisory committees; Janssen: Membership on an entity’s Board of Directors or advisory committees; CTI BioPharma: Membership on an entity’s Board of Directors or advisory committees; Galecto: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Novartis: Membership on an entity’s Board of Directors or advisory committees, Other: Support for attending meetings, Research Funding; Galacteo: Membership on an entity’s Board of Directors or advisory committees; Celgene/BMS: Membership on an entity’s Board of Directors or advisory committees, Research Funding.
