On November 3, 2023 OncoNano Medicine, Inc. reported positive preclinical data describing the effective delivery of interleukin-12 (IL-12) with the ON-BOARD platform technology at the 38th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (Press release, OncoNano Medicine, NOV 3, 2023, View Source [SID1234636890]).
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The study findings show that encapsulation of a therapeutic IL-12 fusion protein (IL-12Fc) for tumor specific delivery and pH-dependent activation was achieved using the ON-BOARD polymeric micelle technology. The study also found that ON-BOARD significantly improved the tolerability of IL-12Fc, as compared to unencapsulated IL-12. The encapsulated IL-12Fc demonstrated potent anti-tumor efficacy and durable anti-tumor memory in the MC38 colorectal cancer model. ONM-412, the development product candidate with the IL-12 encapsulated in the ON-BOARD polymeric micelle system, is advancing through IND-enabling activities.
"These findings underscore the potential application of the ON-BOARD polymeric micelle system for the delivery of IL-12 as an anti-tumor agent," said Tian Zhao, PhD, Vice President of Research and Development at OncoNano. "We look forward to the continued development of ONM-412 and the ONBOARD platform as a potential technology for the targeted delivery of therapeutics to benefit cancer patients."
The data presented demonstrated that:
ON-BOARD enables murine and human IL-12Fc encapsulation with favorable stability and pH-responsive IL-12 bioactivity in vitro in a HEK reporter assay and in primary cell IFNγ induction. Compared to a protease cleavable masked IL-12, the ON-BOARD formulation shows rapid and complete activation over a short period of time.
ON-BOARD encapsulated IL-12Fc exhibited potent anti-tumor efficacy and prolonged survival in MC38 tumor-bearing animals with long-term memory effect.
ON-BOARD formulation demonstrated effective IL-12 signaling in the tumor as evidenced by activation of CD8 T cells and NK cells; increased levels of IFNγ were seen in the tumor but not systemic circulation.
Reduced systemic exposure was observed with ON-BOARD encapsulated IL-12Fc with a significant improvement in the tolerability as evidenced by reduced body weight loss, normal plasma transaminase levels for liver function, reduced splenomegaly, and reduced systemic free IL-12 levels and IL-12 related cytokines when compared to unencapsulated IL-12Fc.
Presentation Details
TITLE: Encapsulation of IL-12 with an ultra pH-sensitive tumor delivery platform improves tolerability and promotes antitumor response in a preclinical model
PRESENTER: Jason Miller, Ph.D., Associate Director, Research Pipeline Development, OncoNano Medicine
POSTER NUMBER: 1147-B