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Raptamer-Drug Conjugates as Molecularly Targeted Cancer Therapeutics

A Champions AACR 2023 Poster


COF-01 is a validated target in patient-derived tumors

We recently identified COF-01 (designated COF-01 as the proprietary code name) to be upregulated in many tumor samples derived from patients with non-small cell lung cancer (NSCLC) and head and neck (H&N) cancer. This dataset was established from DIA-label free quantitative proteomic characterization of a large bank of low passage Patient-derived Xenograft (PDX) models. Importantly, the majority of these PDX models are derived from patients who were treated with, and progressed on, standard of care (SoC) therapy, suggesting overexpression of COF-01 in patient populations of high unmet medical need. Subsequent immunohistochemistry (IHC) evaluation of COF-01 in these tumor samples validated the findings from proteomics.

Targeted cancer therapy: Antibody-drug conjugates

Antibody-drug conjugates (ADCs) are a class of therapeutics that include an antibody moiety for tumor targeting, and a drug payload tethered to the antibody through a chemical linker. Unlike chemotherapy, ADCs are intended to target and kill tumor cells while sparing healthy cells. While ADCs have scored some notable successes, the development of efficacious ADCs still presents considerable challenges. The use of aptamers as a targeting moiety holds the promise of building on the success of ADCs and overcoming challenges for targeted anti-cancer therapy.

Raptamer-drug conjugates as a novel strategy for COF-01-targeted anti-cancer therapeutics

We have generated next-generation ssDNA aptamers (Raptamers) using a novel approach that utilizes our proprietary bead-based oligonucleotide librariesRaptamers contain side chain modifications of amino acid functional groups that can significantly enhance their binding affinity and specificity. Our bead-based technology contains 10unique sequences and each bead carries ~5 million copies of a single sequence. The bead-based selection of Raptamers can be completed between 1-2 weeks. Raptamers that can bind tumor antigens such as COF-01, with high affinity and specificity are well-suited for development of Raptamer-drug conjugates (RapDCs). We have developed a RapDC that can induce targeted killing of COF-01-positive human cancer cells in vitro.

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