Background Despite substantial progress observed in the field of targeted therapies for cancer, there is still a major unmet clinical need for truly personalized medicine approaches. Aummune’s innovative proprietary technology enables a personalized anti-cancer treatment based on a process of selecting and identifying specific functional aptamers – structured single-stranded DNA (ssDNA) oligonucleotides, that are able to bind a large variety of targets with high affinity and specificity.
Methods The Bispecific Personalized Aptamer is comprised of two ssDNA oligonucleotides arms joined together by a dimerization site. One arm of the Bispecific Personalized Aptamer is the outcome of Aummune’s innovative platform,1 identifying functional aptamer sequences with the ability to kill tumor target cells, while leaving healthy tissue intact. The second arm is a constant aptamer sequence that binds to cytotoxic T lymphocytes. The two aptamer arms of the bispecific structure are bridged together by complementary sequences that form a CpG- rich domain designed to induce TLR9-mediated Antigen Presenting Cells (APCs) stimulation.
Results We have demonstrated a successful identification of a personalized aptamer arm using HCT116 colon carcinoma cells as a target. When hybridized to the constant, T cell engager arm, the bispecific entity has demonstrated potent yet selective tumor cell death induction. The Bispecific Aptamer has been further shown to significantly attenuate HCT116 tumor growth in vivo, an effect that was translated into a benefit to survival of treated mice.
Conclusions We have provided a proof-of-concept for Aummune’s platform ability to identify an effective functional personalized aptamer, which did not harm healthy cells. The Bispecific Aptamer’s exerted function in vitro has translated into a significant effect in vivo. Based on the personal approach and multiplicity of modes of action, the Bispecific Personalized Aptamer could have an effect in a broad spectrum of cancer indications.
Mamet N, et al. Commun Biol. 2020
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