Chimeric Antigen Receptor T-cell therapy (CAR T-cell), a type of immunotherapy called adoptive cell therapy, has demonstrated remarkable clinical efficacy in hematological malignancies. However, some barriers such as poor T cell effector function, lack of proliferation, and limited persistence prevent CARs from reaching their full curative potential.
STK-009, an orthogonal IL-2 ligand developed by Synthekine, improved the efficacy and durability of SYNCAR-001, its CD-19 targeted CAR-T cell therapy modified with an orthogonal IL-2 receptor.
The data were delivered during the annual meeting of the American Association for Cancer Research (AACR), held virtually April 10 – 15, 2021, in a poster presentation by Paul-Joseph Aspuria, Ph.D., of Synthekine.
“While CAR-T therapies have proven to be very effective in treating hematological malignancies, the lack of sustained activity and CAR-T cell persistence limits their full therapeutic potential in lymphoma,” said Martin Oft, M.D., chief development officer at Synthekine.
“The presented data demonstrate our orthogonal IL-2 system is well-positioned to overcome these shortcomings. STK-009 demonstrates the ability to expand CAR-Ts in vivo in pre-clinical models, allowing for a lower starting dose of CARs while achieving deep and durable efficacy with the possibility to re-expand resting CARs long after the initial transfer. We look forward to advancing STK-009 and SYNCAR-001 and filing an IND for the program in 2021.”
In both disseminated and subcutaneous RAJI lymphoma models in mice evaluating the efficacy of STK-009 with SYNCAR-001, STK-009 dosing drove increased levels of circulating SYNCAR-001 cells, resulting in complete responses. STK-009 expanded both CAR-T effector cells and stem cell memory cells, resulting in deep initial responses and long-term immune surveillance.
Data on STK-009 from a multiple-ascending dose study in non-human primates were also presented, showing STK-009 was well tolerated, had long exposure, and had no effect on cells expressing only the wild-type IL-2 receptor. A copy of the poster is available on Synthekine’s website.
“Selectivity of this orthogonal IL-2 ligand is fundamental, as more promiscuous activity on bystander cells could lead to systemic toxicity and limit the therapeutic potential of this combined treatment,” Aspuria said.
“Based on the data we presented, we are optimistic about the potential for STK-009 and SYNCAR-001 to overcome hurdles faced by CD19 cell therapy today,” he concluded.
 Aspuria PJP, Vivona S, Bauer M, Semana M, Ratti N, McCauley S, Riener R, De Waal Malefyt R, et al. OrthoCARs: Engineered human IL-2/IL-2Rb orthogonal pairs selectively enhance CAR T cell antitumor efficacy by driving T cell expansion and fitness. Abstract #1512. Presented at: American Association of Cancer Research (AACR); held April 10 – 15, 2021.[Poster][Abstract]
Featured image: Before COVID-19 – Attendees during the Opening Plenary of the 2019 annual meeting of the American Association for Cancer Research. Photo courtesy: © 2019 – 2021 AACR/Used with permission