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Expansion of Human Peripheral Blood γδ T Cells using Zoledronate
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Preclinical evaluation of an innovative anti-TAM approach based on zoledronate-loaded erythrocytes

Raffaella Sabatino1, Serafina Battistelli2, Mauro Magnani1

  • 1Department of Biomolecular Sciences, Section of Biochemistry and Molecular Biology, University of Urbino "Carlo Bo", via A. Saffi 2, 61029, Urbino, PU, Italy.

Drug Delivery and Translational Research
|July 18, 2018
PubMed

Insights

Zoledronate-loaded red blood cells (RBCs) effectively reduce tumor-associated macrophages (TAMs) and inhibit tumor growth in mice. This RBC-based drug delivery system shows promise for cancer therapy by targeting TAMs.

Area of Science:

  • Immunology
  • Oncology
  • Pharmacology

Background:

  • Tumor-associated macrophages (TAMs) play a crucial role in promoting tumor growth, metastasis, and drug resistance.
  • Targeting TAMs is a promising strategy for cancer therapy.
  • Zoledronate, a bisphosphonate, has demonstrated effects on TAM functions.

Purpose of the Study:

  • To evaluate the anti-tumor effects of zoledronate encapsulated in red blood cells (RBCs).
  • To investigate the impact of single and repeated administrations of zoledronate-loaded RBCs on TAMs and tumor growth in a murine mammary carcinoma model.

Main Methods:

  • Administration of zoledronate-loaded RBCs and free zoledronate to mice with mammary carcinoma.
  • Quantification of TAMs in tumor mass.
  • Assessment of tumor growth rate.
  • Evaluation of spleen macrophage depletion.
  • Analysis of Th1 cytotoxic response via IgG2a/IgG1 ratio.

Main Results:

  • Zoledronate-loaded RBCs significantly reduced TAMs in the tumor microenvironment, unlike free zoledronate.
  • Repeated administration of zoledronate-loaded RBCs significantly reduced tumor growth rate.
  • The anti-tumor effect was associated with early depletion of spleen macrophages.
  • A Th1-biased cytotoxic response was observed in mice treated with zoledronate-loaded RBCs.

Conclusions:

  • Zoledronate-loaded RBCs are effective in reducing TAMs and inhibiting tumor growth.
  • This drug delivery system shows potential as a therapeutic strategy for cancer by indirectly depleting TAMs.
  • The findings underscore the importance of macrophages in cancer progression and highlight the suitability of zoledronate-loaded RBCs for cancer treatment.
Keywords:
4T1 cell lineDrug delivery systemsMammary carcinomaRed blood cellsTumor-associated macrophagesZoledronate

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