Simultaneous assessment of drug mechanisms and infusion reactions

Study involving the Immuneed platform highlights the value in simultaneous assessment of drug mechanisms and infusion reactions.

The Immuneed platform, which utilizes fresh, circulating human blood, is central to a new paper published in International Immunopharmacology. The study detailed in the paper explored the donor-specific immune effector signatures of chronic lymphoid lymphoma (CLL) patients in response to anti-CD20. On a wider level, however, the study indicates the potential in analyzing multiple mechanisms and risk factors at the same time. The study, in which Immuneed cooperated with Uppsala Univ., Uppsala Univ. Hospital and the Univ. of Southamptom, looked at anti-CD20 – an antibody that kills B-cells as part of cancer treatment – because of its known risk of triggering cytokine release syndrome (CRS) in CLL patients. In clinical evaluations, the risk of anti-CD20 -induced CRS has been shown to correlate with the patient’s tumor burden. Further, the traditional preclinical assays using peripheral blood mononuclear cells (PBMCs) or other purified cells,  have failed to illustrate the same risk profile. To explore the potential for more effective in vitro testing, the researchers utilized Immuneed’s platform based on fresh, circulating whole blood. A critical factor in the choice was the platform’s ability to simultaneously assess antibody-dependent cellular cytotoxicity (ADCC) and complement-mediated cellular cytotoxicity (CDC), as both mechanisms are integral to anti-CD20’s mode of action. The study confirmed not only a relationship between ADCC and CRS response in CLL patients, but also the increased potency of CDC when ADCC is blocked.

“The anti-CD20 study illustrates how the Immuneed platform can assess multiple functions and risk in the same assay,” says Immuneed’s Erika Fletcher, Head of Research & Development, who is among the co-authors of the paper. ”In the case of anti-CD20, both ADCC and CDC can lead to desirable effects, but ADCC is tied to CRS risk in CLL patients.”

Mark Cragg, Professor of Experimental Cancer Research at the University of Southampton, and another co-author of paper, offers his thoughts about the Immuneed platform. “I have been involved with antibody-based therapeutics for over 20 years, largely seeking to understand mechanisms of action and resistance,” he says. “When we explore this, it is crucially important to have the most physiologically relevant tools and methods. Immuneed’s system harbors all of the immune cells present in the circulation as well as the many proteins and metabolites available in serum, and so can provide a unique dimension to the analysis not always captured by alternative assays based on purified cell or serum components.” To read the full publication, visit “Profiling of donor-specific immune effector signatures in response to anti-CD20 in a human whole blood loop assay using blood from CLL patients”

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