Trp2 Peptide Vaccine Adjuvanted with (R)-DOTAP Inhibits Tumor Growth in an Advanced Melanoma Model

Abstract

Previously we have shown cationic lipid (R)-DOTAP as the immunologically active enantiomer of the DOTAP racemic mixture, initiating complete tumor regression in an exogenous antigen model (murine cervical cancer model). Here, we investigate the use of (R)-DOTAP as an efficacious adjuvant delivering an endogenous antigen in an aggressive murine solid tumor melanoma model. (R)-DOTAP/Trp2 peptide complexes showed decreasing size and charge with increasing peptide concentration, taking a rod-shape at highest concentrations. The particles were stable for at 2 weeks at 4°C. A dose of 75nmol Trp2 (formulated in (R)-DOTAP) was able to show statistically significant tumor growth delay compared to lower doses of 5 and 25nmol which were no different than untreated tumors. (R)-DOTAP/Trp2 (75nmol) treated mice also showed increased T cell IFN-γ secretion after restimulation with Trp2, as well as CTL activity in vivo. This vaccination group also showed the highest population of functionally active tumor-infiltrating lymphocytes, indicated by IFN-γ secretion after restimulation with Trp2. Thus, (R)-DOTAP has shown the ability to break tolerance as an adjuvant. Its activity to enhance immunogenicity of other tumor associated antigens should be studied further.

Cargo-Free Nanoparticles Containing Cationic Lipids Induce Reactive Oxygen Species and Cell Death in HepG2 Cells

“…4) Similar to siRNA delivery, polypeptide-DOTAP systems are important in the studies of cancer therapies and therefore various formulations containing DOTAP have been developed. 4,5) Regarding the molecular mechanisms through with polypeptide-loaded cationic NPs function as cancer vaccines, E7 peptide-DOTAP NPs have been shown to induce the production of reactive oxygen species (ROS) in bone marrow-derived dendritic cells. 6) In addition, cationic liposomes containing DOTAP or stearylamine have been suggested to induce ROS and concomitant apoptosis and/or toxicity in cells.…”

Design of pH-sensitive polymer-modified liposomes for antigen delivery and their application in cancer immunotherapy

“…73 1,2-Dioleoyl-3-dimethylammoniumpropane (DOTAP) is the most-studied cationic lipid that might be used as an adjuvant molecule. [73][74][75][76] Actually, DOTAP is recognized by G protein-coupled receptors (GPCRs)…”

Nanomaterials for cancer immunotherapy

“…For example, cationic lipid (R)-DOTAP is an immunologically active enantiomer of the DOTAP racemic mixture, and could initiate a strong immune response in an exogenous antigen model [70, 71]. Specific functionalization and different lateral side dimensions of graphene and carbon-based nanomaterials showed distinct impacts on immune cells, which would induce a specific activation of dendritic cells and monocytes and serve as a nanoadjuvant for the development of an effective antitumor immune response [72–75].…”