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The head of the CAR T cell antibody can recognize and target the growth factor in its tumor microenvironment.
The FDA approved an investigational new drug application (IND) that allows clinical trials to be done on MUC1*-CAR-1XX (huMNC2-CAR22; Minerva Biotechnologies) for patients with metastatic breast cancer.1 This is the first CAR T that targets muk 1 star ((MUC1*), huMNC2-CAR44).
MUC1* is a growth factor receptor that is responsible for driving the growth and metastasis of most solid tumor cancers.1 Investigators observed recently during their research that this transmembrane cleavage product may actually drive the growth of approximately 93% of breast cancers.2
“The ability of our antibody to bind specifically to the cancerous form of MUC1 without binding to MUC1 on normal tissues is a real breakthrough,” said Cynthia Bamdad, CEO, Minerva Biotechnologies, in a press release.2
At present, MUC1*-CAR-1XX is being studied in the NCT04020575 trial. It is the first-in-human trial to study a CAR T cell therapy which targets MUC1* in patients with MUC1* reactive tumors. MUC1*-CAR-1XX works by binding to the tumor’s ectopic site, which will become exposed after cleavage.2
MUC1*-CAR-1XX has displayed early signs of safety and efficacy in this ongoing clinical trial. Patients have been shown to shift from progressive disease to stable disease and partial response. Further, CAR T cells are showing signs of expansion.1
But MUC1*-CAR-1XX must create a durable response in patients, which means the CAR T cell must overcome one of the most common threats to CAR T cell efficacy—CAR T cell exhaustion. Exhaustion is 1 of 2 major hurdles that the 1XX mutation will solve,” the Minerva CEO said in the press release.1 The second hurdle is “failure to kill the low antigen expressing cells.”1
The “1XX” mutation is a combination of 4 tyrosine to phenylalanine mutations. Effectively, it will slow signal of the T cell’s CD3-z domain. In turn, this can increase its persistence against the tumor’s MUC1* growth factor.1 The CAR T cell is being studied as a treatment against multiple forms of metastatic breast cancers.1
“We have a broad, deep pipeline that includes next generation CAR Ts, with enhanced in vivo persistence, and the ability to target cells with much lower antigen density, allowing us to challenge the persistent issues seen elsewhere in the field,” Michael Crowther, chief business officer, Minerva, said in a press release.2
“Together with our MUC1* antibodies that recognize an epitope only available on cancer cells, huMNC2-CAR22 (MUC1*-CAR-1XX) promises to be a big leap ahead in our fight against cancers,” said Bamdad in the press release.1
References
1. Minerva Biotechnologies. Minerva Biotechnologies Gets FDA Approval of IND for a MUC1*-CAR-1XX with Increased Persistence and Ability to Kill Low Antigen Expressing Cells for Treatment of Solid Tumor Cancers. Business Wire. News Release. January 9, 2023. Accessed on January 10, 2023. https://www.businesswire.com/news/home/20230109005010/en
2. Minerva Biotechnologies. Minerva Biotechnologies Announces Opening 1st-In-Human Phase I/II Trial of a MUC1* Targeting CAR T for Metastatic Breast Cancers at City of Hope. Business Wire. News Release. February 1, 2022. Accessed on January 10, 2023. https://www.businesswire.com/news/home/20220201005200/en/Minerva-Biotechnologies-Announces-Opening-1st-In-Human-Phase-III-Trial-of-a-MUC1*-Targeting-CAR-T-for-Metastatic-Breast-Cancers-at-City-of-Hope