Adoptive cell transfer therapy with ex vivo primed peripheral lymphocytes in combination with anti-PDL1 therapy effectively inhibits triple-negative breast cancer growth and metastasis

Odd L. Gammelgaard*, Mikkel G. Terp, Alexei F. Kirkin, Simone Johansen, Sofie Traynor, Henriette Vever, Per Guldberg, Annette R. Kodahl, Morten F. Gjerstorff, Henrik J. Ditzel*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Background: Adoptive cell transfer cancer immunotherapy holds promise for treating disseminated disease, yet generating sufficient numbers of lymphocytes with anti-cancer activity against diverse specificities remains a major challenge. We recently developed a novel procedure (ALECSAT) for selecting, expanding and maturating polyclonal lymphocytes from peripheral blood with the capacity to target malignant cells. Methods: Immunodeficient mice were challenged with triple-negative breast cancer cell lines or patient-derived xenografts (PDX) and treated with allogeneic or autologous ALECSAT cells with and without anti-PDL1 therapy to assess the capacity of ALECSAT cells to inhibit primary tumor growth and metastasis. Results: ALECSAT mono therapy inhibited metastasis, but did not inhibit primary tumor growth or prolong survival of tumor-bearing mice. In contrast, combined ALECSAT and anti-PDL1 therapy significantly inhibited primary tumor growth, nearly completely blocked metastasis, and prolonged survival of tumor-bearing mice. Conclusions: Combined ALECSAT and anti-PDL1 therapy results in favorable anti-cancer responses in both cell line-derived xenograft and autologous PDX models of advanced triple-negative breast cancer.

Original languageEnglish
Article number6
JournalMolecular Cancer
Volume23
Number of pages16
ISSN1476-4598
DOIs
Publication statusPublished - 6. Jan 2024

Keywords

  • Adoptive cell transfer therapy
  • ALECSAT
  • Anti-PDL1
  • Cellular cancer therapy
  • Triple-negative breast cancer
  • Immunotherapy, Adoptive
  • Humans
  • Triple Negative Breast Neoplasms/therapy
  • Antibodies, Monoclonal, Humanized
  • Animals
  • Lymphocytes
  • Mice
  • Disease Models, Animal

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