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CCL22-based peptide vaccines induce anti-cancer immunity by modulating tumor microenvironment

Inés Lecoq1,2, Katharina L Kopp1, Marion Chapellier1

  • 1Department of Research and Development, IO Biotech ApS, Copenhagen, Denmark.

Oncoimmunology
|September 2, 2022
PubMed

Insights

Targeting the immunosuppressive chemokine CCL22 with peptide vaccines stimulates anti-tumor immune responses. This approach enhances T-cell infiltration and reduces tumor growth, offering a novel cancer immunotherapy strategy.

Area of Science:

  • Immunology
  • Oncology
  • Vaccine Development

Background:

  • CCL22 is an immunosuppressive chemokine that recruits regulatory T cells (Tregs) via the CCL22:CCR4 axis, hindering anti-cancer immunity.
  • CCL22 plays a significant role in immune suppression across various cancer types.
  • Previous research demonstrated that CCL22-specific T cells from cancer patients could eliminate CCL22-expressing tumor cells.

Purpose of the Study:

  • To provide a preclinical rationale for developing CCL22-targeting immunotherapies.
  • To investigate the immunogenicity and anti-tumor efficacy of CCL22-derived peptide vaccines.
  • To analyze the impact of CCL22 peptide vaccination on the tumor immune microenvironment.

Main Methods:

  • Vaccination of mice (BALB/c and C57BL/6) with CCL22-derived peptides.
  • Assessment of CCL22-specific T-cell responses via interferon-γ secretion (ex vivo).
  • Evaluation of anti-tumor efficacy in syngeneic mouse tumor models.
  • Analysis of immune cell infiltration in the tumor microenvironment using multicolor flow cytometry.

Main Results:

  • CCL22 peptide vaccination successfully induced CCL22-specific T-cell responses.
  • Vaccinated mice exhibited reduced tumor growth and prolonged survival.
  • Vaccination altered the tumor immune microenvironment, increasing CD8+ T cell and M1 macrophage infiltration.
  • The CD8/Treg and M1/M2 macrophage ratios were significantly increased post-vaccination.

Conclusions:

  • CCL22 peptide vaccines effectively modulate the tumor immune microenvironment.
  • Targeting CCL22 with peptide vaccines augments anti-tumor immune responses.
  • This study supports the development of CCL22-targeting peptide vaccines as a novel cancer immunotherapy.
Keywords:
CCL22immune modulationimmunotherapypeptide vaccinetumor microenvironment

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