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Perspectives

New Life for Immunotoxin Cancer Therapy

Raffit Hassan, Christine Alewine and Ira Pastan
Raffit Hassan
1Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland.
2Thoracic and GI Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
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  • For correspondence: pastani@mail.nih.gov hassanr@mail.nih.gov
Christine Alewine
1Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland.
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Ira Pastan
1Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland.
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  • For correspondence: pastani@mail.nih.gov hassanr@mail.nih.gov
DOI: 10.1158/1078-0432.CCR-15-1623 Published March 2016
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Abstract

Immunotoxins are targeted anticancer therapeutics that kill cancer cells using a cytotoxic bacterial toxin payload. Their development for use in solid tumor malignancies was delayed due to issues with their immunogenicity and limited therapeutic window. However, new research has rejuvenated the field. Coadministration with a lymphocyte-depleting regimen of pentostatin and cyclophosphamide can delay antidrug antibody formation, increasing the number of treatment cycles that patients can receive and resulting in durable responses in heavily pretreated patients. In addition, a new generation of immunotoxin molecules with reduced immunogenicity and nonspecific toxicity has been developed through protein engineering techniques, and one has recently entered the clinic. In preclinical studies in mouse models, these new agents are effective against many tumor types as single agents, and also produce synergistic antitumor responses in combination with chemotherapy. These new immunotoxins have renewed excitement in the field and may prove a promising addition to the targeted therapy repertoire. Clin Cancer Res; 22(5); 1055–8. ©2015 AACR.

  • Received July 8, 2015.
  • Revision received September 9, 2015.
  • Accepted September 30, 2015.
  • ©2015 American Association for Cancer Research.
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Clinical Cancer Research: 22 (5)
March 2016
Volume 22, Issue 5
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New Life for Immunotoxin Cancer Therapy
Raffit Hassan, Christine Alewine and Ira Pastan
Clin Cancer Res March 1 2016 (22) (5) 1055-1058; DOI: 10.1158/1078-0432.CCR-15-1623

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New Life for Immunotoxin Cancer Therapy
Raffit Hassan, Christine Alewine and Ira Pastan
Clin Cancer Res March 1 2016 (22) (5) 1055-1058; DOI: 10.1158/1078-0432.CCR-15-1623
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Clinical Cancer Research
eISSN: 1557-3265
ISSN: 1078-0432

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