GLA monotherapy for use in cancer treatment
Inventors
Paya Cuenca, Carlos V. • Ter Meulen, Jan Henrik
Assignees
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Publication Number
US-10342815-B2
Publication Date
2019-07-09
Expiration Date
Abstract
The present disclosure relates generally to compositions and methods for treating cancer with a glucopyranosyl lipid A (GLA) in the absence of antigen.
Core Innovation
The invention relates to treating cancer in a mammal by administering by intratumoral injection an effective amount of a composition comprising glucopyranosyl lipid A (GLA) and a pharmaceutically acceptable carrier or excipient. The composition does not comprise antigen, and GLA is defined by a formula or a pharmaceutically acceptable salt thereof with specific structural definitions for the substituents and phosphate, hydroxyl, and alkyl features.
The described approach links antigen-free GLA administration to innate immune system activity through targeting of TLR4. Immune response readouts are described in terms of cytokines and cytotoxic T-cell responses after treatment. Pharmaceutical carriers and formulation types are described to include aqueous formulations, oil-in-water or water-in-oil emulsions, liposomes, micelles, and microparticles.
The document reports treatment outcomes in cancer models and human data, including reduced tumor size and improved survival in in vivo B16 melanoma models after treatment of established tumors with GLA-SE. It further describes enhanced efficacy when GLA-SE is used in combination with immune checkpoint inhibitors (anti-PD(L)1 and anti-CTLA4) and with anti-CD40. For clinical data, it describes preliminary Phase I observations in Merkel cell carcinoma, including a complete response in a patient after intratumoral GLA-SE.
Claims Coverage
The document includes two independent claims. Across these claims, the inventive coverage is centered on antigen-free, intratumoral injection of a defined GLA composition formulated with a pharmaceutically acceptable carrier or excipient, with one claim directed to treating cancer and the other directed to reducing tumor size; a key shared inventive limitation is that the composition does not comprise antigen.
Antigen-free intratumoral GLA composition for treating cancer
Administering by intratumoral injection an effective amount of a composition comprising GLA of a defined formula (or a pharmaceutically acceptable salt thereof) and a pharmaceutically acceptable carrier or excipient, wherein the composition does not comprise antigen.
Antigen-free intratumoral GLA composition for reducing tumor size
Administering by intratumoral injection an effective amount of a composition comprising GLA of a defined formula (or a pharmaceutically acceptable salt thereof) and a pharmaceutically acceptable carrier or excipient, wherein the composition does not comprise antigen, to reduce the size of a tumor in a mammal.
Both independent claims require an antigen-free composition comprising structurally defined GLA and a pharmaceutically acceptable carrier or excipient, administered by intratumoral injection. One claim recites treating cancer in a mammal, and the other recites reducing tumor size, using the same core composition limitations and antigen exclusion.
Stated Advantages
Reduced tumor size in in vivo B16 melanoma models after treatment of established tumors with GLA-SE.
Improved survival in in vivo B16 melanoma models after treatment of established tumors with GLA-SE.
Enhanced efficacy when GLA-SE is combined with immune checkpoint inhibitors (anti-PD(L)1 and anti-CTLA4).
Enhanced efficacy when GLA-SE is combined with anti-CD40.
A complete response in a patient with Merkel cell carcinoma after intratumoral GLA-SE in preliminary Phase I observations.
Documented Applications
Treating cancer in a mammal by intratumoral injection of an antigen-free GLA composition, including for solid tumors.
Reducing the size of a tumor in a mammal by intratumoral injection of an antigen-free GLA composition.
In vivo B16 melanoma model use, including treatment of established tumors with GLA-SE.
Clinical use in Merkel cell carcinoma, including preliminary Phase I observations with intratumoral GLA-SE.
Combination use in follicular low grade NHL with intratumoral GLA, anti-CTLA4, and rituximab.
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