Tumor repolarization by an advanced liposomal drug delivery system provides a potent new approach for chemo-immunotherapy
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Tumor repolarization by an advanced liposomal drug delivery system provides a potent new approach for chemo-immunotherapy. / Ringgaard, L.; Melander, F.; Eliasen, R.; Henriksen, J. R.; Jølck, R. I.; Engel, T. B.; Bak, M.; Fliedner, F. P.; Kristensen, K.; Elema, D. R.; Kjaer, A.; Hansen, A. E.; Andresen, T. L.
I: Science Advances, Bind 6, Nr. 36, eaba5628, 2020.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Tumor repolarization by an advanced liposomal drug delivery system provides a potent new approach for chemo-immunotherapy
AU - Ringgaard, L.
AU - Melander, F.
AU - Eliasen, R.
AU - Henriksen, J. R.
AU - Jølck, R. I.
AU - Engel, T. B.
AU - Bak, M.
AU - Fliedner, F. P.
AU - Kristensen, K.
AU - Elema, D. R.
AU - Kjaer, A.
AU - Hansen, A. E.
AU - Andresen, T. L.
N1 - Publisher Copyright: © 2020 The Authors, some rights reserved.
PY - 2020
Y1 - 2020
N2 - Immunosuppressive cells in the tumor microenvironment allow cancer cells to escape immune recognition and support cancer progression and dissemination. To improve therapeutic efficacy, we designed a liposomal oxaliplatin formulation (PCL8-U75) that elicits cytotoxic effects toward both cancer and immunosuppressive cells via protease-mediated, intratumoral liposome activation. The PCL8-U75 liposomes displayed superior therapeutic efficacy across all syngeneic cancer models in comparison to free-drug and liposomal controls. The PCL8-U75 depleted myeloid-derived suppressor cells and tumor-associated macrophages in the tumor microenvironment. The combination of improved cancer cell cytotoxicity and depletion of immunosuppressive populations of immune cells is attractive for combination with immune-activating therapy. Combining the PCL8-U75 liposomes with a TLR7 agonist induced immunological rejection of established tumors. This combination therapy increased intratumoral numbers of cancer antigen-specific cytotoxic T cells and Foxp3-T helper cells. These results are encouraging toward advancing liposomal drug delivery systems with anticancer and immune-modulating properties into clinical cancer therapy.
AB - Immunosuppressive cells in the tumor microenvironment allow cancer cells to escape immune recognition and support cancer progression and dissemination. To improve therapeutic efficacy, we designed a liposomal oxaliplatin formulation (PCL8-U75) that elicits cytotoxic effects toward both cancer and immunosuppressive cells via protease-mediated, intratumoral liposome activation. The PCL8-U75 liposomes displayed superior therapeutic efficacy across all syngeneic cancer models in comparison to free-drug and liposomal controls. The PCL8-U75 depleted myeloid-derived suppressor cells and tumor-associated macrophages in the tumor microenvironment. The combination of improved cancer cell cytotoxicity and depletion of immunosuppressive populations of immune cells is attractive for combination with immune-activating therapy. Combining the PCL8-U75 liposomes with a TLR7 agonist induced immunological rejection of established tumors. This combination therapy increased intratumoral numbers of cancer antigen-specific cytotoxic T cells and Foxp3-T helper cells. These results are encouraging toward advancing liposomal drug delivery systems with anticancer and immune-modulating properties into clinical cancer therapy.
U2 - 10.1126/sciadv.aba5628
DO - 10.1126/sciadv.aba5628
M3 - Journal article
C2 - 32917608
AN - SCOPUS:85090917020
VL - 6
JO - Science advances
JF - Science advances
SN - 2375-2548
IS - 36
M1 - eaba5628
ER -
ID: 269499759