Abstract
Alpha tocopheryl succinate (α-TOS) is a non-toxic vitamin E analog under study for its anti-cancer properties. In an earlier study, we showed that α-TOS, when used in combination with non-matured dendritic cells (nmDC) to treat pre-established tumors, acts as an effective adjuvant. In this study, we have used vesiculated α-TOS (Vα-TOS), a more soluble form of α-TOS that is relevant for clinical use, in combination with dendritic cells to treat pre-established murine tumors. We demonstrate that Vα-TOS kills tumor cells in vitro and inhibits the growth of pre-established murine lung carcinoma (3LLD122) as effectively as α-TOS. The combination of Vα-TOS plus non-matured or TNF-α-matured DC is more effective at inhibiting the growth of established tumors than Vα-TOS alone. We also observed that Vα-TOS induces expression of heat shock proteins in tumor cells and that co-incubation of non-matured DC with lysate derived from Vα-TOS-treated tumor cells leads to DC maturation evidenced by up-regulation of co-stimulatory molecules and secretion of IL-12p70. This study therefore demonstrates the immunomodulatory properties of Vα-TOS that may account for its adjuvant effect when combined with DC vaccines to treat established tumors.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 166-177 |
| Number of pages | 12 |
| Journal | Cancer Immunology, Immunotherapy |
| Volume | 55 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 2006 |
Fingerprint
Keywords
- α-tocopheryl succinate
- Dendritic cell
- Heat shock proteins
- Immunotherapy
- Vaccine
ASJC Scopus subject areas
- Cancer Research
- Immunology
- Oncology
Cite this
Vesiculated alpha-tocopheryl succinate enhances the anti-tumor effect of dendritic cell vaccines. / Ramanathapuram, Lalitha V.; Hahn, Tobias; Graner, Michael W.; Katsanis, Emmanuel; Akporiaye, Emmanuel T.
In: Cancer Immunology, Immunotherapy, Vol. 55, No. 2, 02.2006, p. 166-177.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Vesiculated alpha-tocopheryl succinate enhances the anti-tumor effect of dendritic cell vaccines
AU - Ramanathapuram, Lalitha V.
AU - Hahn, Tobias
AU - Graner, Michael W.
AU - Katsanis, Emmanuel
AU - Akporiaye, Emmanuel T.
PY - 2006/2
Y1 - 2006/2
N2 - Alpha tocopheryl succinate (α-TOS) is a non-toxic vitamin E analog under study for its anti-cancer properties. In an earlier study, we showed that α-TOS, when used in combination with non-matured dendritic cells (nmDC) to treat pre-established tumors, acts as an effective adjuvant. In this study, we have used vesiculated α-TOS (Vα-TOS), a more soluble form of α-TOS that is relevant for clinical use, in combination with dendritic cells to treat pre-established murine tumors. We demonstrate that Vα-TOS kills tumor cells in vitro and inhibits the growth of pre-established murine lung carcinoma (3LLD122) as effectively as α-TOS. The combination of Vα-TOS plus non-matured or TNF-α-matured DC is more effective at inhibiting the growth of established tumors than Vα-TOS alone. We also observed that Vα-TOS induces expression of heat shock proteins in tumor cells and that co-incubation of non-matured DC with lysate derived from Vα-TOS-treated tumor cells leads to DC maturation evidenced by up-regulation of co-stimulatory molecules and secretion of IL-12p70. This study therefore demonstrates the immunomodulatory properties of Vα-TOS that may account for its adjuvant effect when combined with DC vaccines to treat established tumors.
AB - Alpha tocopheryl succinate (α-TOS) is a non-toxic vitamin E analog under study for its anti-cancer properties. In an earlier study, we showed that α-TOS, when used in combination with non-matured dendritic cells (nmDC) to treat pre-established tumors, acts as an effective adjuvant. In this study, we have used vesiculated α-TOS (Vα-TOS), a more soluble form of α-TOS that is relevant for clinical use, in combination with dendritic cells to treat pre-established murine tumors. We demonstrate that Vα-TOS kills tumor cells in vitro and inhibits the growth of pre-established murine lung carcinoma (3LLD122) as effectively as α-TOS. The combination of Vα-TOS plus non-matured or TNF-α-matured DC is more effective at inhibiting the growth of established tumors than Vα-TOS alone. We also observed that Vα-TOS induces expression of heat shock proteins in tumor cells and that co-incubation of non-matured DC with lysate derived from Vα-TOS-treated tumor cells leads to DC maturation evidenced by up-regulation of co-stimulatory molecules and secretion of IL-12p70. This study therefore demonstrates the immunomodulatory properties of Vα-TOS that may account for its adjuvant effect when combined with DC vaccines to treat established tumors.
KW - α-tocopheryl succinate
KW - Dendritic cell
KW - Heat shock proteins
KW - Immunotherapy
KW - Vaccine
UR - http://www.scopus.com/inward/record.url?scp=27944499761&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=27944499761&partnerID=8YFLogxK
U2 - 10.1007/s00262-005-0016-7
DO - 10.1007/s00262-005-0016-7
M3 - Article
C2 - 16041582
AN - SCOPUS:27944499761
VL - 55
SP - 166
EP - 177
JO - Cancer Immunology and Immunotherapy
JF - Cancer Immunology and Immunotherapy
SN - 0340-7004
IS - 2
ER -