A recombinant antibody-interleukin 2 fusion protein suppresses growth of hepatic human neuroblastoma metastases in severe combined immunodeficiency mice

Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9626-30. doi: 10.1073/pnas.91.20.9626.

Abstract

A genetically engineered fusion protein consisting of a human/mouse chimeric anti-ganglioside GD2 antibody (ch14.18) and recombinant human interleukin 2 (rhIL-2) was tested for its ability to target rhIL-2 to tumor sites and stimulate immune effector cells sufficiently to achieve effective tumor cell lysis in vivo. The ch14.18-IL-2 fusion protein proved more effective than equivalent doses of rhIL-2 in suppressing dissemination and growth of human neuroblastoma in an experimental hepatic metastases model of scid (severe combined immunodeficiency) mice reconstituted with human lymphokine-activated killer cells. The ch14.18-IL-2 fusion protein was also more proficient than equivalent doses of rhIL-2 in prolonging the life-span of these animals. This recombinant antibody-cytokine fusion protein may prove useful for future treatment of GD2-expressing human tumors in an adjuvant setting.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies / therapeutic use
  • Cytotoxicity, Immunologic
  • Gangliosides / immunology*
  • Humans
  • Immunotherapy, Adoptive*
  • Interleukin-2 / therapeutic use*
  • Killer Cells, Lymphokine-Activated / immunology
  • Liver Neoplasms / pathology
  • Liver Neoplasms / prevention & control
  • Liver Neoplasms / secondary*
  • Liver Neoplasms / therapy
  • Mice
  • Mice, SCID
  • Neuroblastoma / pathology
  • Neuroblastoma / prevention & control
  • Neuroblastoma / secondary*
  • Neuroblastoma / therapy
  • Recombinant Fusion Proteins / therapeutic use*
  • Transplantation, Heterologous

Substances

  • Antibodies
  • Gangliosides
  • Interleukin-2
  • Recombinant Fusion Proteins
  • ganglioside, GD2