On December 23, 2021 Synthekine Inc., an engineered cytokine therapeutics company, reported the publication of preclinical data for its lead cell therapy program using the orthogonal IL-2 receptor/ligand system in Science Translational Medicine (Press release, Synthekine, DEC 23, 2021, View Source [SID1234597677]). This system uses a lock and key approach, wherein an orthogonal IL-2 receptor (the "lock") is engineered into an adoptive T cell therapy (ACT) so that it can be selectively stimulated by an orthogonal IL-2 ligand (the "key"). This creates the ability to employ IL-2 signaling completely independent of the endogenous IL-2 receptor/ligand, allowing for controlled and enhanced in vivo expansion of ACTs without toxicities emerging from the indiscriminate activation of the endogenous immune system. The published data shows STK-009, the orthogonal IL-2 ligand, enables the control of cell expansion and activation of a CD19 CAR-T cell therapy which expresses the orthogonal IL-2 receptor (SYNCAR-001) in preclinical models of human lymphoma. The publication, titled "An Orthogonal IL-2 and IL-2Rß System Drives Persistence and Activation of CAR-T Cells and Clearance of Bulky Lymphoma" can be accessed here.
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"CAR-T cell therapies are an important emerging modality in the treatment of cancer," said Martin Oft, M.D., chief development officer at Synthekine. "However, the limitations of these therapies must be addressed to expand their utility. The data described in this paper demonstrates the potential of STK-009 + SYNCAR-001 to address key limitations of current CD19 CAR-T cell therapies by increasing the expansion, activity, and persistence of CAR-T cells in vivo to improve the depth and durability of responses."
CAR-T cell therapies targeting CD19, a cell-surface antigen present on B cells, are approved by the FDA for the treatment of advanced, refractory hematologic malignancies such as lymphoma. CD19 CAR-T cell therapies can lead to long-term remissions and even cures for patients. However, median progression free survival is limited to less than 6 months in lymphoma patients, and approximately half of all patients who initially respond will relapse.
Synthekine designed its orthogonal IL-2 system to address these limitations of CD19 CAR-T cells and other adoptive cell therapies. Results from the preclinical studies show that treatment with STK-009 resulted in both systemic and intratumoral expansion and activation of SYNCAR-001 cells. As a result, even with substantially reduced cell doses, SYNCAR-001 together with STK-009 treatment were able to drive complete responses in large lymphoma lesions.
Synthekine expects to file an IND for STK-009 + SYNCAR-001 in 2022. The company is also exploring its orthogonal IL-2 system with other CAR-T targets and additional ACT approaches, particularly in the solid tumor setting.