Fate Therapeutics Plans Trials Testing Off-the-shelf NK Cell Therapy for Lymphoma, Leukemia

Fate Therapeutics Plans Trials Testing Off-the-shelf NK Cell Therapy for Lymphoma, Leukemia

Fate Therapeutics has been cleared by the U.S. Food and Drug Administration (FDA) to initiate clinical studies evaluating FT596, its off-the-shelf cell-based immunotherapy designed to target multiple tumor proteins.

The company plans to start testing FT596 for the treatment of B-cell lymphoma and chronic lymphocytic leukemia, either alone or in combination with CD20-targeted monoclonal antibodies.

FT596 derives from an induced pluripotent stem cell (iPSC) line, which are essentially stem cells derived from adult, specialized cells. These “induced” stem cells can give rise to any type of human cell for therapeutic purposes, including cancer-fighting immune cells.

FT596, specifically, is a type of chimeric chimeric antigen receptor (CAR) natural killer (NK) cell cancer immunotherapy, where cells were genetically engineered to have three different anti-cancer components, in addition to the normal features of NK immune cells.

In addition to carrying Fate’s proprietary CAR targeting the CD19 protein — produced by virtually all lymphoma and leukemia cells — cells also have a high-affinity, small sequence of the CD16 receptor, which enhances the ability of immune cells to target malignant B-cells while augmenting the effects of antibody-mediated cancer cell death.

FT596 also carries the interleukin-15 receptor fusion, or IL-15RF, which consists of a potent protein complex that promotes survival, proliferation, and activation of both NK and anti-cancer T-cells.

All combined, FT596’s unique features are intended to maximize potency and minimize toxicity in treated patients.

“FT596 is a ground-breaking product candidate with the potential to supplant current-generation patient-specific and allogeneic CAR19 T-cell immunotherapies, which recognize only one antigen and fail to address the significant risk of relapse due to antigen escape,” Scott Wolchko, president and CEO of Fate Therapeutics, said in a news release.

“We believe the product candidate’s engineered functionality, coupled with its ability to be cost-effectively administered on-demand in multiple treatment cycles, will deliver a deeper and more durable response to patients compared to single-antigen targeted CAR19 T-cells,” he added.

Data from preclinical studies demonstrated that all three anti-cancer activities of FT596 can function at the same time, resulting in enhanced potential to fight cancer cells.

Further experiments showed that a combination of FT596 with the anti-B cell antibody rituximab (brand name Rituxan, among others) was more effective at killing a mixed culture of CD19-positive and negative tumor cells than standard CAR-T cell therapy.

Supported by these findings, Fate said that FT596 may elicit a deeper and more durable response against B-cell lymphomas and leukemias.

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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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