Delivery of Cytokines by Liposomes. III. Liposome- Encapsulated GM-CSF and TNF-?? Show Improved Pharmacokinetics and Biological Activity and Reduced Toxicity in Mice

Targeting Dendritic Cells with Antigen-Containing Liposomes

“…In addition, evidence suggests that liposome-associated IFN-␥ is biologically active and that IFN-␥ can be encapsulated within liposomes and as well can bind to the outer surface of liposomes (38,39). Similar findings have been reported with GM-CSF (40). These attributes permit liposome-associated LPS, GM-CSF, and IFN-␥ to interact with DC surface receptors and also provide the possibility that upon the binding, disruption, and/or fusion of the targeted SL or PMV, with the membrane of DCs, the SL-encapsulated agent that is released is then able to interact with receptors on DCs.…”

Pegylated liposomal tumor necrosis factor‐α results in reduced toxicity and synergistic antitumor activity after systemic administration in combination with liposomal doxorubicin (Doxil®) in soft tissue sarcoma‐bearing rats

“…These findings are in agreement with previous results in which the toxicity of TNF was reduced up to 7-fold after encapsulation in large multilamellar liposomes. 5 We speculate from our in vitro results with the TNF-sensitive tumor cell line WEHI-164 that first, TNF is only slowly released from the liposomes and is not bioavailable when encapsulated, resulting in lower toxicity, and second, increased accumulation at the tumor site results in higher local TNF levels and improved tumor response.…”

“…22 The prolonged circulation time and augmented tumor accumulation of liposomal TNF, which result from the encapsulation of TNF in pegylated liposomes, provides a depot of encapsulated TNF in tumor tissue and sustained release of the cytokine. Kedar et al 5 have demonstrated that release of TNF encapsulated in large multilamellar liposomes was required for the cytokine to be active. Rapid release of TNF from liposomes would therefore be necessary when the liposomes exhibit a relatively short circulation time.…”

“…One way of diminishing systemic toxicity, and at the same time increasing delivery of TNF to the tumor site, is the encapsulation of the cytokine in liposomes with long-circulating characteristics such as pegylated (STEALTH) liposomes. 4,5 It was previously demonstrated that agents encapsulated in pegylated liposomes exhibit a prolonged blood residence time and an increased tumor accumulation compared with free agents. 4,6,7 We have shown that encapsulation of TNF in pegylated liposomes (TNF-PEGL) results in a blood residence half-time of 22 hr (compared with 45 min for the free agent) and a 14-fold increase in the area under the curve (AUC) in the tumor.…”

Enhancement of tumor thermal therapy using gold nanoparticle–assisted tumor necrosis factor-α delivery

“…Therefore, there is a need for selective tumor delivery of TNF-a to minimize systemic toxicity. Delivery of TNF-a using a liposomal delivery system has shown some promise in animal cancer models but requires very high doses of the drug (17,18). Gene therapy with TNF-a has also been explored, but the limitations are lack of selective transduction of tumor cells to minimize toxicity and efficient gene transfer to every cell to prevent proliferation of nontransduced cells (19 -22).…”