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Tumor-specific macrophage targeting through recognition of retinoid X receptor beta

Tang Tang1, Yushuang Wei1, Jinyoung Kang2

  • 1Department of Pharmaceutics, University of Minnesota, Minneapolis, MN 55455, USA; Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.

Journal of Controlled Release : Official Journal of the Controlled Release Society
|March 16, 2019
PubMed

Insights

Researchers identified a novel peptide, CRV, that targets tumor macrophages specifically. This discovery offers a new way to deliver cancer therapies directly to tumors, avoiding healthy tissues and improving treatment efficacy.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Macrophages are crucial in cancer progression but targeting them specifically for therapy is challenging.
  • Current macrophage-targeting strategies lack tumor specificity, leading to off-target effects in healthy organs.

Purpose of the Study:

  • To identify and characterize novel tools for tumor-specific macrophage targeting.
  • To validate a peptide (CRV) and its receptor (retinoid X receptor beta) for targeted delivery in cancer therapy.

Main Methods:

  • Systemic administration of CRV peptide in tumor-bearing mice.
  • In vivo and in vitro binding assays to assess CRV specificity for tumor macrophages.
  • Identification and validation of the CRV receptor using antibody-based approaches.
  • Evaluation of CRV's ability to enhance nano-carrier delivery.

Main Results:

  • CRV selectively homes to tumors and binds preferentially to tumor-associated macrophages.
  • Retinoid X receptor beta (RXRB) was identified as the cell surface receptor for CRV on tumor macrophages.
  • Anti-RXRB antibodies also demonstrated tumor-selective macrophage binding.
  • CRV facilitated improved delivery of nano-carriers into solid tumors and tumor macrophages.

Conclusions:

  • CRV is a novel targeting tool for tumor macrophages, with RXRB as its specific receptor.
  • This discovery provides a potential platform for developing targeted macrophage-modulatory cancer therapies.
  • Targeting tumor macrophages via CRV/RXRB may enhance therapeutic efficacy and reduce side effects.
Keywords:
Cargo deliveryRXR beta targetingTumor homingTumor-associated macrophages

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