CD200 mimetic aptamer PEG-M49 markedly increases the therapeutic effects of pegylated liposomal doxorubicin in a mouse model of metastatic breast carcinoma: an effect independent of CD200 receptor 1.

Erin N., Dilmaç S., CURRY A., Duymuş Ö., Tanriover G., Prodeus A., ...Daha Fazla

Cancer immunology, immunotherapy : CII, cilt.69, ss.103-114, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 69
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1007/s00262-019-02444-3
  • Dergi Adı: Cancer immunology, immunotherapy : CII
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, EMBASE, MEDLINE
  • Sayfa Sayıları: ss.103-114
  • Anahtar Kelimeler: Metastasis, Breast cancer, CD200, Aptamer, Doxorubicin, MDSC, CD4(+)CD8(+) T-CELLS, SUPPRESSOR-CELLS, CANCER CELLS, INFLAMMATION, EXPRESSION, INDUCTION, ALPHA, IMMUNOGENICITY, LYMPHOCYTES, IMMUNITY
  • Akdeniz Üniversitesi Adresli: Evet

Özet

We previously reported that CD200 overexpression in the host decreases progression and metastasis of the highly aggressive metastatic 4THM breast carcinoma. We have explored a possible synergistic interaction between the CD200 mimetic PEG-M49 and pegylated liposomal doxorubicin (Peg-Dox) in wild-type CD200 knockout (CD200(-/-)) and CD200 Receptor 1 knockout (CD200R1(-/-)) mice for the first time. A 4THM breast carcinoma model and three groups of BALB/c mice (wild type, CD200(-/-) and CD200R1(-/-)) were used. Five days after injection of tumor cells, mice were injected with Peg-Dox (ip, once a week) and PEG-M49 or a control aptamer (iv, every 3 days). Necropsies were performed either 12 (mid-point) or 24 (endpoint) days after injection and the extent of tumor growth, visceral metastasis and changes in the tumor-directed immune response were evaluated. PEG-M49 and Peg-Dox co-treatment induced complete tumor regression and loss of macroscopic lung metastasis in four out of seven WT mice. This synergistic anti-tumoral effect is thought to be due to Peg-M49-induced inhibition of Gr1 + CD11b + cells and Peg-Dox-induced increases in tumor-infiltrating CD8 + and CD8CD4 double-positive cells. Similar changes were observed in CD200R1(-/-) mice indicating that the primary effects of Peg-M49 are mediated by non-CD200R1 receptors. We also demonstrated for the first time that tumor growth, metastasis, and tumor infiltrating GR1 + CD11b + cells were markedly increased in CD200R1(-/-) mice, indicating an anti-inflammatory and protective role of CD200. CD200 mimetics might be a safe and effective immunomodulatory treatment in conjunction with classical chemotherapeutics for therapy of aggressive metastatic breast carcinoma.