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CCR4 Antagonists Inhibit Treg Trafficking into the Tumor Microenvironment

John M Ketcham1, Lisa A Marshall1, Oezcan Talay1

  • 1FLX Bio, Inc., 561 Eccles Avenue, South San Francisco, California 94080, United States.

ACS Medicinal Chemistry Letters
|October 23, 2018
PubMed

Insights

Naturally occurring regulatory T cells (Treg) can hinder anti-tumor responses in cancer immunotherapy. New small molecule CCR4 antagonists effectively block Treg recruitment to the tumor microenvironment.

Area of Science:

  • Immunology
  • Oncology

Background:

  • Regulatory T cells (Treg) expressing CD4, CD25, and FOXP3 suppress anti-tumor immunity.
  • Treg cells are recruited to the tumor microenvironment (TME) via chemokines CCL17 and CCL22, mediated by CCR4.
  • This Treg recruitment can diminish the effectiveness of immuno-oncology (IO) treatments.

Discussion:

  • The study focuses on the role of Treg cells in the TME and their impact on IO therapy efficacy.
  • It highlights the chemokine receptor CCR4 as a key mediator of Treg cell infiltration.
  • The development of small molecule antagonists targeting CCR4 is presented as a novel therapeutic strategy.

Key Insights:

  • Potent, orally bioavailable small molecule antagonists of CCR4 have been developed.
  • These antagonists effectively block the recruitment of Treg cells into the TME.
  • This blockade has the potential to enhance anti-tumor responses in patients undergoing IO therapy.

Outlook:

  • Further preclinical and clinical studies are warranted to evaluate the efficacy of CCR4 antagonists in combination with IO agents.
  • This approach may offer a new strategy to overcome resistance to cancer immunotherapy.
  • Optimizing the delivery and dosage of these small molecules will be crucial for therapeutic success.

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