Clinically Approved Immunotoxins Targeting Hematological Cancers: "The Best of Both Worlds"

Yasmine Rashad^1,2Eckhard Alt³Reza Izadpanah³Xuebin Qin^2,4Stephen E Braun^5,6*

• ¹Tulane Heart and Vascular Institute, School of Medicine, Tulane University, New Orleans, United States
• ²Department of Microbiology and Immunology, School of Medicine, Tulane University, New Orleans, Louisiana, United States
• ³Applied Stem Cell Laboratory, Heart and Vascular Institute, Department of Medicine, Tulane University School of Medicine, New Orleans, United States
• ⁴Division of Comparative Pathology, Tulane National Primate Research Center, School of Medicine, Tulane University, Covington, Louisiana, United States
• ⁵Department of Pharmacology, School of Medicine, Tulane University, New Orleans, Louisiana, United States
• ⁶Division of Immunology, Tulane National Primate Research Center, Covington, Louisiana, United States

Abstract Hematological malignancies contribute significantly to overall cancer burden. Certain subtypes, such as hairy cell leukemia (HCL), are chronic and known for leaving residual disease after first-line therapy; others, like blastic plasmacytoid dendritic cell neoplasm (BPDCN), are aggressive and associated with poor prognosis. Although cornerstone interventions such as radiation and chemotherapy are efficiently used to treat some malignant blood neoplasms, these treatments are often limited by resistance, relapse, lack of enduring disease-free survival/complete remission, and systemic effects. Immunotoxins were developed to increase tumor targeting and have evolved into recombinant immunotoxins (RITs). These novel bioengineered chimeras genetically combine robust cytotoxins with targeted localized binding domains. In this review, we analyze three FDA-approved RITs, moxetumomab pasudotox, tagraxofusp, and denileukin diftitox, that utilize bacterial toxins from Pseudomonas and Corynebacterium diphtheriae to treat refractory/relapsed (R/R) HCL, BPDCN, adult R/R cutaneous T-cell lymphoma (CTCL), respectively. We reviewed the comprehensive safety profiles and observed complications associated with these fusion proteins; and finally, we discuss potential risk management options that may enhance their clinical outcome. Overall, RITs have been efficacious, and researchers continue to extend these findings to other indications.