NOF to Exhibit and Present a poster at SITC 2025 (Nov 7-8)

In recent years, Antibody-drug conjugates (ADCs) are one of the fastest growing therapeutic modalities in the field of cancer treatment. A high drug-to-antibody ratio (DAR) is a desirable characteristic because it increases the efficacy. However, preparing high DAR ADCs often lead to issues such as aggregation and decreased antibody stability in the blood due to hydrophobicity of the drugs. One approach to solving this issue is the use of hydrophilic linkers.

We developed a pendant type PEG linker which have two PEG chains between different functional groups. In this study, we prepared ADCs using cleavable pendant type PEG linkers incorporating a ValCit dipeptide for drug release and varying the PEG chain length to 4, 8, or 12 (hereafter referred to as PEG4, PEG8, and PEG12, respectively), and compared their efficacy.

Interleukin-2 (IL-2) is a well-established immune-oncology agent that activates CD8+ T cells. However, its therapeutic efficacy is limited due to its short half-life and IL-2 receptor alpha (IL-2Rα) capability. Moreover, the activation of CD8+ T cells by IL-2 is especially suppressed in the tumor microenvironment (TME) due to the acidic condition. Therefore, long-acting IL-2, which reduces IL-2Rα capability and enhances cytotoxic T lymphocyte (CTL) activity of CD8+ T cells, is desired to enhance the therapeutic efficacy of IL-2.

Here, we developed IL-2 mutein conjugated by releasable PEG that improves the pharmacokinetic profile and selectively activates CD8+ T cells residing in lymphoid organs and the tumor microenvironment without inducing significant serious side effects.