Antibody-based delivery of IL2 and cytotoxics eradicates tumors in immunocompetent mice.

Abstract

Antibody-drug conjugates are increasingly being used for cancer therapy, but little is known about their ability to promote anticancer immunity, which may lead to long-lasting remissions. We investigated the therapeutic effect of antibody-based pharmacodelivery of cemadotin, a cytotoxic drug, and IL2, a strong proinflammatory cytokine. Using the F8 antibody, which selectively localizes to the tumor neovasculature, combination treatment led to tumor eradication, in a process dependent on CD8(+) T cells and natural killer cells in the C1498 syngeneic mouse model of acute myelogenous leukemia. The clinical combination of antibody-drug conjugates and antibody-cytokine proteins should be facilitated by their orthogonal toxicity profiles.

• Authors: Katrin L Gutbrodt, Giulio Casi, Dario Neri
• Journal: Molecular cancer therapeutics (Mol Cancer Ther) Vol. 13 Issue 7 Pg. 1772-6 (Jul 2014) ISSN: 1538-8514 [Electronic] United States
• PMID: 24759429 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2014 American Association for Cancer Research.

Chemical References

• Antibodies
• Antineoplastic Agents
• Immunotoxins
• Interleukin-2
• Oligopeptides
• cemadotin

Topics

• Animals
• Antibodies (immunology)
• Antineoplastic Agents (administration & dosage)
• CD4-Positive T-Lymphocytes (drug effects, immunology)
• CD8-Positive T-Lymphocytes (drug effects, immunology)
• Disease Models, Animal
• Female
• Immunotoxins (administration & dosage, immunology)
• Interleukin-2 (administration & dosage)
• Killer Cells, Natural (drug effects, immunology)
• Leukemia, Myeloid, Acute (drug therapy, immunology)
• Mice
• Mice, Inbred C57BL
• Oligopeptides (administration & dosage)
• Xenograft Model Antitumor Assays