IL7-Fc Enhances the Efficacy of Adoptive T Cell Therapy under Lymphopenic Conditions in a Murine Melanoma Model

Cells. 2021 Aug 7;10(8):2018. doi: 10.3390/cells10082018.

Abstract

Adoptive cell therapy (ACT) using tumor-reactive T cells is a promising form of immunotherapy to specifically target cancer. However, the survival and functional maintenance of adoptively transferred T cells remains a challenge, ultimately limiting their efficacy. Here, we evaluated the use of recombinant IL7-Fc in ACT. In a lymphopenic murine melanoma model, IL7-Fc treatment led to the enhanced inhibition of tumor growth with an increased number of adoptively transferred CD8+ T cells in tumor tissue and tumor-draining lymph nodes. Additionally, IL7-Fc further enhanced anti-tumor responses that were induced by recombinant human IL2 in the same mouse model. In contrast, in an immunocompetent murine melanoma model, IL7-Fc dampened the anti-tumor immunity. Further, IL7-Fc decreased the proliferation of adoptively transferred and immune-activated tumor-reactive CD8+ T cells in immunocompetent mice by inducing the massive expansion of endogenous T cells, thereby limiting the space for adoptively transferred T cells. Our data suggest that IL7-Fc is principally beneficial for enhancing the efficacy of tumor-reactive T-cells in lymphopenic conditions for the ACT.

Keywords: IL-2; IL-7; adoptive cell therapy; immunotherapy; lymphopenia; melanoma; recombinant IL7-Fc; tumor-specific T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow / drug effects
  • Bone Marrow / immunology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Humans
  • Immunoglobulin Fc Fragments / genetics
  • Immunoglobulin Fc Fragments / immunology*
  • Immunoglobulin Fc Fragments / metabolism
  • Immunotherapy, Adoptive / methods*
  • Interleukin-7 / genetics
  • Interleukin-7 / immunology*
  • Interleukin-7 / metabolism
  • Leukocyte Count
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Lymphopenia / immunology*
  • Lymphopenia / metabolism
  • Melanoma, Experimental / genetics
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Myeloid Cells / cytology
  • Myeloid Cells / drug effects
  • Myeloid Cells / immunology
  • Recombinant Fusion Proteins / administration & dosage*
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / metabolism

Substances

  • Immunoglobulin Fc Fragments
  • Interleukin-7
  • Recombinant Fusion Proteins