CHDR demonstrates translational value of LPS challenge model for early phase oncology drug development

Demonstrating meaningful pharmacodynamic (PD) activity early in oncology drug development remains challenging. While dose selection is increasingly expected to be driven by biological effects rather than toxicity alone, suitable human in vivo models are still limited.

In a study published in Clinical Pharmacology & Therapeutics, CHDR researchers show that an intravenous lipopolysaccharide (LPS) challenge in healthy participants can be used to induce and measure oncology‑relevant pharmacodynamic responses in both peripheral blood and bone marrow.

Healthy male volunteers received a low intravenous dose of LPS (1 or 2 ng/kg) to transiently activate inflammatory and oncogenic signalling pathways. Blood and bone marrow samples were analysed using an integrated translational approach, including immunophenotyping, multiplex cytokine profiling, bulk RNA sequencing and immunohistochemistry. The LPS challenge was safe and well tolerated, including when combined with bone marrow sampling.

Transcriptomic analyses revealed the induction of multiple oncology‑relevant, druggable targets. In total, 91 targets were identified in blood and 24 in bone marrow. Notably, the oncogenic transcription factor MYC was upregulated in bone marrow in a dose‑dependent manner and confirmed at the protein level.

These findings demonstrate how controlled immune activation in healthy participants can support PD‑driven decision‑making early in oncology development, providing translational insight ahead of patient studies.

The study was fully designed, conducted and funded by CHDR in Leiden, The Netherlands, in collaboration with academic partners.

Read the full publication here: Intravenous Lipopolysaccharide Challenge in Healthy Participants Reveals Pharmacodynamic Markers in Blood and Bone Marrow for Early-Phase Oncology Drug Development | CHDR