90 Y-NM600 targeted radionuclide therapy induces immunologic memory in syngeneic models of T-cell Non-Hodgkin's Lymphoma

Commun Biol. 2019 Feb 26;2:79. doi: 10.1038/s42003-019-0327-4. eCollection 2019.

Abstract

Finding improved therapeutic strategies against T-cell Non-Hodgkin's Lymphoma (NHL) remains an unmet clinical need. We implemented a theranostic approach employing a tumor-targeting alkylphosphocholine (NM600) radiolabeled with 86Y for positron emission tomography (PET) imaging and 90Y for targeted radionuclide therapy (TRT) of T-cell NHL. PET imaging and biodistribution performed in mouse models of T-cell NHL showed in vivo selective tumor uptake and retention of 86Y-NM600. An initial toxicity assessment examining complete blood counts, blood chemistry, and histopathology of major organs established 90Y-NM600 safety. Mice bearing T-cell NHL tumors treated with 90Y-NM600 experienced tumor growth inhibition, extended survival, and a high degree of cure with immune memory toward tumor reestablishment. 90Y-NM600 treatment was also effective against disseminated tumors, improving survival and cure rates. Finally, we observed a key role for the adaptive immune system in potentiating a durable anti-tumor response to TRT, especially in the presence of microscopic disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Female
  • Humans
  • Immunologic Memory / immunology
  • Immunologic Memory / radiation effects*
  • Lymphoma, T-Cell / diagnostic imaging
  • Lymphoma, T-Cell / immunology
  • Lymphoma, T-Cell / radiotherapy*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, SCID
  • Positron-Emission Tomography / methods*
  • Tissue Distribution / immunology
  • Tissue Distribution / radiation effects
  • Tumor Burden / immunology
  • Tumor Burden / radiation effects
  • Xenograft Model Antitumor Assays / methods
  • Yttrium Radioisotopes / blood
  • Yttrium Radioisotopes / pharmacokinetics
  • Yttrium Radioisotopes / therapeutic use*

Substances

  • Yttrium Radioisotopes
  • Yttrium-86