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Merck
  • Combination therapy with liposomal doxorubicin and liposomal vaccine containing E75, an HER-2/neu-derived peptide, reduces myeloid-derived suppressor cells and improved tumor therapy.

Combination therapy with liposomal doxorubicin and liposomal vaccine containing E75, an HER-2/neu-derived peptide, reduces myeloid-derived suppressor cells and improved tumor therapy.

Life sciences (2020-04-10)
Parvin Zamani, Jamshid Gholizadeh Navashenaq, Manouchehr Teymouri, Maryam Karimi, Mohammad Mashreghi, Mahmoud Reza Jaafari
ABSTRACT

Myeloid-derived suppressor cells (MDSCs) are immunosuppressive cells causing resistance to immunotherapies in cancer tumors. In the current study, various immunogenic and therapeutic features of the combination therapies with non-liposomal Doxorubicin (Dox) and the E75 immunogenic peptide (Pep), derived from the human epidermal receptor-2 (HER-2), are investigated in parallel with their liposomal formulations (Lip-Dox (Doxil®) and Lip-Pep). Therefore, triple injection doses of Lip-Pep were preceded with Dox and Lip-Dox injections in TUBO/breast tumor-bearing BALB/c mice. Chemotherapy with either Dox or Lip-Dox reduced the frequency of MDSCs, the level of reactive oxygen species (ROS), and MDSCs-associated genes of Arg1, iNOS, S100A8, S100A9. Whereas Lip-Pep + Dox and Lip-Pep + Lip-Dox treatments synergistically potentiated the immunized splenocytes to produce INF-γ and enhanced the frequency of the anti-tumor CD8+ and CD4+ T cells as opposed to both chemotherapy and immunotherapy regimens. Chemo-immunotherapy increased the number of tumor-infiltrating lymphocytes (TILs) and reduced the level of CD25+ FoxP3+ T regulatory cells. Taken together, chemo-immunotherapy was the optimum treatment for the limitation of tumor progression as they targeted more cancer-related immune players.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
L-α-Phosphatidylethanolamine, dioleoyl, ≥99% (GC), ≥98% (TLC), lyophilized powder
Avanti
18:0 PC (DSPC), Avanti Research - A Croda Brand
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18:1 (Δ9-Cis) PE (DOPE), Avanti Research - A Croda Brand
Avanti
18:1 (Δ9-Cis) PE (DOPE), Avanti Research - A Croda Brand
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18:0 PC (DSPC), Avanti Research - A Croda Brand
Avanti
DSPE-PEG(2000) Maleimide, Avanti Research - A Croda Brand 880126C
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18:0 PG, Avanti Research - A Croda Brand
Avanti
DSPE-PEG(2000) Maleimide, Avanti Research - A Croda Brand 880126P, powder