CCR4‐IL2 bispecific immunotoxin is more effective than brentuximab for targeted therapy of cutaneous T‐cell lymphoma in a mouse CTCL model
Zhaohui Wang,
Jihong Ma,
Huiping Zhang,
Rashmi Ramakrishna,
Danielle Mintzlaff,
David W. Mathes,
Elizabeth A. Pomfret,
M. Scott Lucia,
Dexiang Gao,
Bradley M. Haverkos,
Zhirui Wang
Affiliations
Zhaohui Wang
Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine University of Colorado Anschutz Medical Campus Aurora CO USA
Jihong Ma
Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine University of Colorado Anschutz Medical Campus Aurora CO USA
Huiping Zhang
Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine University of Colorado Anschutz Medical Campus Aurora CO USA
Rashmi Ramakrishna
Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine University of Colorado Anschutz Medical Campus Aurora CO USA
Danielle Mintzlaff
Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine University of Colorado Anschutz Medical Campus Aurora CO USA
David W. Mathes
Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine University of Colorado Anschutz Medical Campus Aurora CO USA
Elizabeth A. Pomfret
Division of Transplant Surgery, Department of Surgery, School of Medicine University of Colorado Anschutz Medical Campus Aurora CO USA
M. Scott Lucia
Department of Pathology, School of Medicine University of Colorado Anschutz Medical Campus Aurora CO USA
Dexiang Gao
Department of Pediatrics, University of Colorado Cancer Center Biostatistics and Bioinformatics Shared Resource University of Colorado Anschutz Medical Campus Aurora CO USA
Bradley M. Haverkos
University of Colorado Hospital, School of Medicine University of Colorado Anschutz Medical Campus Aurora CO USA
Zhirui Wang
Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine University of Colorado Anschutz Medical Campus Aurora CO USA
Cutaneous T‐cell lymphoma (CTCL) encompasses two main subtypes: mycosis fungoides and Sezary syndrome. Global response rates for the systemic treatment of mycosis fungoides and Sezary syndrome are approximately 30%, and none of these treatments are thought to be curative. C–C chemokine receptor type 4 (CCR4) and CD25 are encouraging targets for the treatment of CTCL and are individually targeted by mogamulizumab and denileukin diftitox, respectively. We developed a novel CCR4‐IL2 bispecific immunotoxin (CCR4‐IL2 IT) targeting both CCR4 and CD25. CCR4‐IL2 IT demonstrated superior efficacy against CCR4+CD25+CD30+ CTCL in an immunodeficient NSG mouse tumor model. Investigative New Drug‐enabling studies of CCR4–IL2 IT are ongoing, including Good Manufacturing Practice production and toxicology studies. In this study, we compared the in vivo efficacy of CCR4‐IL2 IT versus the US Food and Drug Administration–approved drug, brentuximab, using an immunodeficient mouse CTCL model. We demonstrated that CCR4–IL2 IT was significantly more effective in prolonging survival than brentuximab, and combination treatment of CCR4–IL2 IT and brentuximab was more effective than brentuximab or CCR4–IL2 IT alone in an immunodeficient NSG mouse CTCL model. Thus, CCR4–IL2 IT is a promising novel therapeutic drug candidate for CTCL treatment.
