biostudies-literatureUnknown20(5)Sampson JFTakeda Development Center Americas, Inc.Recombinant interferon alpha (IFNα) has been used to treat cancer patients for over 30 years; however, its clinical utility has been limited by a narrow therapeutic index. Given the recognized anti-tumor and immunomodulatory impacts of IFNα, the development of novel strategies to harness these attributes while minimizing associated toxicity could provide significant benefit for patients. The concept of attenuating IFNα binding affinity for its receptor was conceived to address this challenge and led to the development of CD38-targeted Attenukine™, a CD38-targeted antibody attenuated IFNα immunocytokine. In this study, we sought to delineate the effects of targeting AttenukineTM specifically to tumor cells and/or immune cells using an antibody to CD38, a cell surface glycoprotein expressed PloS onee0321622https://www.ebi.ac.uk/biostudies/studies/S-EPMC12047799biostudies-literatureCD38-targeted attenuated interferon alpha immunocytokine activates both innate and adaptive immune cells to drive anti-tumor activity.PMC12047799Hinthorne ASyed SBjorck PZhang DChattopadhyay NPogue SZhang YCollins SZhang HSampson JFBi MCurley MfalseCD38-targeted attenuated interferon alpha immunocytokine activates both innate and adaptive immune cells to drive anti-tumor activity.Recombinant interferon alpha (IFNα) has been used to treat cancer patients for over 30 years; however, its clinical utility has been limited by a narrow therapeutic index. Given the recognized anti-tumor and immunomodulatory impacts of IFNα, the development of novel strategies to harness these attributes while minimizing associated toxicity could provide significant benefit for patients. The concept of attenuating IFNα binding affinity for its receptor was conceived to address this challenge and led to the development of CD38-targeted Attenukine™, a CD38-targeted antibody attenuated IFNα immunocytokine. In this study, we sought to delineate the effects of targeting AttenukineTM specifically to tumor cells and/or immune cells using an antibody to CD38, a cell surface glycoprotein expressed 2025-01-01T00:00:00Z20252025-06-25T03:06:25.119Z2025-06-25T03:06:25.119ZS-EPMC120477994031522610.1371/journal.pone.0321622