The immunocytokine L19-TNF eradicates sarcomas in combination with chemotherapy agents or with immune check-point inhibitors

Anticancer Drugs. 2020 Sep;31(8):799-805. doi: 10.1097/CAD.0000000000000938.

Abstract

Antibody-cytokine fusion proteins (also called 'immunocytokines') represent an emerging class of biopharmaceutical products, which are being considered for cancer immunotherapy. When used as single agents, pro-inflammatory immunocytokines are rarely capable of inducing complete and durable cancer regression in mouse models and in patients. However, the combination treatment with conventional chemotherapy or with other immune-stimulatory agents typically increases the therapeutic efficacy of immunocytokines. In this article, we describe combination treatments of a tumor-targeting antibody-cytokine fusion protein based on the L19 antibody (specific to a splice isoform of fibronectin) fused to murine tumor necrosis factor with standard chemotherapy (dacarbazine, trabectedin or melphalan) or with an immune check-point inhibitor (anti-PD-1) in a BALB/c derived immunocompetent murine model of sarcoma (WEHI-164). All combination treatments led to improved tumor remission compared to single-agent treatments, suggesting that these combination partners may be suitable for further clinical development in sarcoma patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis
  • Cell Proliferation
  • Dacarbazine / administration & dosage
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / administration & dosage*
  • Mice
  • Mice, Inbred BALB C
  • Recombinant Fusion Proteins / administration & dosage
  • Sarcoma / drug therapy*
  • Sarcoma / immunology
  • Sarcoma / pathology
  • Trabectedin / administration & dosage
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies, Monoclonal
  • Immune Checkpoint Inhibitors
  • L19mTNFalpha protein
  • Recombinant Fusion Proteins
  • Dacarbazine
  • Trabectedin