Autologous huMNC2-CAR44 Cells for Breast Cancer Targeting Cleaved Form of MUC1 (MUC1*)
Minerva's clinical trial is now enrolling for metastatic breast cancer.
Minerva Biotechnologies has developed a CAR T (huMNC2-CAR44) that targets the extracellular domain of the clipped form of MUC1 (called MUC1*), which is the form of MUC1 that functions as a growth factor receptor and is present on large percentage of solid tumors, including ~90% of breast tumors. The antibody targeting head of huMNC2-CAR44 specifically recognizes a cancerous form of MUC1* and does not bind to another form of cleaved MUC1 that is present on some normal tissues that also have a rapid turnover. The huMNC2-CAR44 product consists of autologous T cells that are isolated from cancer patients, transduced with a proprietary lentiviral vector backbone manufactured under cGMP, containing sequences for a human leader sequence, humanized MNC2-scFv (MUC1* targeting head), portions of human hinge and transmembrane domains, and human 4-1BB and human CD3-zeta costimulatory domains. In vitro, huMNC2-CAR44 effectively killed a wide range of MUC1* positive cells. Importantly, huMNC2-CAR44 had no effect on cells expressing full-length MUC1 nor MUC1 negative cells and engagement of the huMNC2-CAR44 leads to cell death. In vivo, huMNC2-CAR44 effectively inhibits the growth of MUC1* positive tumors and greatly increased survival in murine models.
This clinical trial will evaluate the safety and antitumor activity of adoptively transferred autologous T cells genetically modified to express a CAR that targets MUC1*, huMNC2-CAR44.
Information about the trial can be found here: https://clinicaltrials.gov/ct2/show/NCT04020575