Formulation of Toll-like Receptor Ligand with Whole Cell Tumor Vaccine to Enhance Anti-tumor Responses

Established reports in literature have shown that the innate immune system can modulate immune responses against cancer. Lipopolysaccharide (LPS), a Toll-like receptor ligand 4 (TLR4), was absorbed onto whole cell tumor vaccine using a liposome formulation. The liposome reagent was titrated with LPS for greater than 95% complex formulation onto whole tumor cells. The LPS absorbed whole tumor cells had been previously modified to secrete genetically modified cerebrospinal fluid (GM-CSF). After absorption, the tumor vaccine was lethally irradiated, and functional analysis was performed in murine model of a poorly immunogenic tumor. The GM-CSF secreting tumor vaccine formulated with LPS showed anti-tumor responses not detectable with GM-CSF secreting tumor vaccines. Description (Set) Proposed Use (Set) LPS is a well known ligand for TLR4 receptors on immune cells, particularly dendritic cells. Their biological function is to stimulate the innate immune system and to modulate adaptive immune system in mammals. This invention adds two new dimensions to the current state of the art in tumor immunology. First, it formulates a TLR4 ligand onto whole cell tumor vaccine. Second, it uses this novel reagent to induce anti-tumor responses in an animal model of a poorly immunogenic tumor with an active tolerance mechanism. This invention can deliver TLR4 ligand locally to the site of tumor to enhance local anti-tumor immune responses and minimize toxicity. The vaccine can be used to treat advanced malignancies amenable for immunotherapeutic treatments and be used to make combinatorial vaccines for complex diseases amenable for immunotherapy.

Inventor(s): Kim, Young

Type of Offer: Licensing

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