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

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-typ...

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Bibliographic Details
Published in:Cancer Immunology, Immunotherapy Immunotherapy, 2020-01, Vol.69 (1), p.103-114
Main Authors: Erin, Nuray, Dilmaç, Sayra, Curry, Anna, Duymuş, Özlem, Tanriover, Gamze, Prodeus, Aaron, Gariepy, Jean, Gorczynski, Reginald M.
Format: Article
Language:English
Subjects:
Animals
Antigens, CD - genetics
Antigens, CD - immunology
Antineoplastic Combined Chemotherapy Protocols - pharmacology
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Aptamers
Aptamers, Nucleotide - pharmacology
Aptamers, Nucleotide - therapeutic use
Breast cancer
Breast carcinoma
Breast Neoplasms - drug therapy
Breast Neoplasms - immunology
Breast Neoplasms - pathology
Cancer Research
CD11b antigen
CD200 antigen
CD8 antigen
Cell Line, Tumor
Disease Models, Animal
Doxorubicin
Doxorubicin - analogs & derivatives
Doxorubicin - pharmacology
Doxorubicin - therapeutic use
Drug Synergism
Female
Humans
Immune response
Immunology
Immunomodulation
Inflammation
Injection
Medicine
Medicine & Public Health
Metastases
Metastasis
Mice
Mice, Inbred BALB C
Mice, Knockout
Oncology
Orexin Receptors - genetics
Orexin Receptors - immunology
Original
Original Article
Polyethylene Glycols - pharmacology
Polyethylene Glycols - therapeutic use
Rodents
Tumor cells
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Summary: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.
ISSN:0340-7004
1432-0851
DOI:10.1007/s00262-019-02444-3