Antibody-based delivery of IL2 and cytotoxics eradicates tumors in immunocompetent mice.
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' Affiliations: Department of Chemistry and Applied Biosciences, ETH Zürich, Zurich; and.
Katrin L
KL
Gutbrodt
Philochem AG, Otelfingen, Switzerland.
Giulio
G
Casi
Authors' Affiliations: Department of Chemistry and Applied Biosciences, ETH Zürich, Zurich; and neri@pharma.ethz.ch.
Dario
D
Neri
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D000922:Immunotoxins / Q000008:administration & dosage* / Q000276:immunology; D007376:Interleukin-2 / Q000008:administration & dosage*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000008:administration & dosage*; D023041:Xenograft Model Antitumor Assays
D000906:Antibodies; D000970:Antineoplastic Agents; D000922:Immunotoxins; D007376:Interleukin-2; D009842:Oligopeptides; C094621:cemadotin