Poseida’s P-BCMA-101 Eliminates Tumors in Mice with Multiple Myeloma, Studies Show

Poseida’s P-BCMA-101 Eliminates Tumors in Mice with Multiple Myeloma, Studies Show

Poseida Therapeutics‘ P-BCMA-101 eradicates tumors in mouse models of multiple myeloma and creates memory T-cells that go on the attack when the disease returns, preclinical trial studies indicate.

The treatment also prolonged the mice’s survival better than other CAR T-cell treatments, the company said. CAR T-cell therapies use patients’ own immune cells to attack cancer.

Poseida presented the findings in a poster session at the American Association for Cancer Research 2017 Annual Meeting in Washington. The study was titled “PiggyBac-manufactured anti-BCMA Centyrin-based CAR-T therapeutic exhibits improved potency and durability.”

“CAR-T therapies have been extremely effective in treating acute lymphoblastic leukemia and have shown promise against multiple myeloma; however, relatively poor potency and durability continue to limit their efficacy,” Eric Ostertag, MD, PhD, chief executive officer of Poseida, said in a press release. “In our recent study being presented at AACR, we report significant improvements in potency and durability with our P-BCMA-101 CAR-T product, compared to results typically seen with competitors’ products in a preclinical multiple myeloma model.”

The improvements were “made possible by our advanced T-cell engineering capabilities that create multiple desirable attributes in CAR-expressing T cells,” Ostertag said.

CAR T-cells are genetically engineered T-cells designed to do a better job of detecting and eliminating cancer cells. The cells are removed from a patient and taken to a lab, where they are modified to express a chimeric antigen receptor, or CAR, that is specific to a cancer protein.

Usually, CAR T-cells are engineered to express an antibody that recognizes the cancer protein. Poseida has developed a new approach that it believes is more stable and less immunogenic — that is, doesn’t induce immune responses against the engineered cells.

The technique involves Centyrin molecules, which work like antibodies, binding to a specific protein.

P-BCMA-101’s T-cells express a BCMA-specific Centyrin. BCMA, or B-cell maturation antigen, is commonly found in myeloma cells and is a promising target for myeloma therapies.

Another innovation that Poseida used in creating P-BCMA-101 was the delivery system. Most CAR T-cell therapies use viral vectors to deliver a CAR gene to T-cells. Poseida scientists use a gene delivery system called piggyBac DNA Modification System, which lets them insert two additional genes in the delivery vehicle.

One gene can be used to shut down T-cell activity when side effects arise. The other gene allows scientists to specifically select T-cells with a BCMA-specific Centyrin in their DNA. Using this gene for selecting cells means that 95 percent of P-BCMA-101’s composition can consist of modified T-cells. The modified T-cell content of other CAR T-cell products ranges from 30 to 50 percent.

P-BCMA-101 reduces tumors in mice within seven days, while untreated mice die within four weeks, according to the preclinical trial studies.

In addition, the response to P-BCMA-101 was durable: it eliminated tumors when mice relapsed. Most mice treated with P-BCMA-101 survived 110 days, twice as long as the 50 days of mice treated with other viral-vector products.

Another important finding was that more than 70 percent of P-BCMA-101 cells displayed stem cell-like memory, allowing memory and effector T-cells to self-renew. Effector T-cells are those that actively respond to a stimulus.

The memory-cell content of products besides P-BCMA-101 is less than 20 percent, suggesting that P-BCMA-101 may reduce the need for subsequent injections in humans.

The researchers also reported that P-BCMA-101 did not show any signs of T-cell exhaustion. That’s important because exhausted T-cells have a reduced ability to eliminate tumor cells.

Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
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Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
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Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.

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