The present disclosure provides pladienolide compounds, pharmaceutical compositions containing such compounds, and pladienolide compounds for use in methods of medical treatment. These compounds may be useful in the treatment of cancer, particularly cancers in which agents that target the spliceosome and mutations therein are known to be useful. Also provided herein are pladienolide compounds for use in methods of treating cancers by administering at least one pladienolide compound disclosed herein and at least one additional therapy

The present invention relates to methods of treating a disease characterised by aberrant cell proliferation (e.g., a cancer) in a human subject in need thereof. In particular, the present invention relates to treating the above conditions by administering a therapeutically effective amount of at least one agent that increases activation of a receptor of at least one type II interferon and/or type I interferon, and administering to the subject at least one agent that inhibits the Hedgehog (Hh) signalling pathway (e.g., Vismodegib). Also provided are pharmaceutical compositions, including controlled release pharmaceutical compositions, containing at least one agent that increases activation of a receptor of at least one type II interferon and/or type I interferon (e.g., a checkpoint inhibitor), an inhibitor of Hh signalling pathway, and a controlled release matrix such as a SiO.sub.2 matrix gel.

The present invention relates to methods of treating a disease characterised by aberrant cell proliferation (e.g., a cancer) in a human subject in need thereof. In particular, the present invention relates to treating the above conditions by administering a therapeutically effective amount of at least one agent that increases activation of a receptor of at least one type II interferon and/or type I interferon, and administering to the subject at least one agent that inhibits the Hedgehog (Hh) signalling pathway (e.g., Vismodegib). Also provided are pharmaceutical compositions, including controlled release pharmaceutical compositions, containing at least one agent that increases activation of a receptor of at least one type II interferon and/or type I interferon (e.g., a checkpoint inhibitor), an inhibitor of Hh signalling pathway, and a controlled release matrix such as a SiO.sub.2 matrix gel.

Methods for generating immune responses using adenovirus vectors that allow multiple vaccinations with the same adenovirus vector and vaccinations in individuals with preexisting immunity to adenovirus are provided.

Embodiments are directed to compositions and methods of treating migraine and related neurological disorders. In certain aspects, methods and compositions are for reducing cortical spreading depression and/or suppressing the neurochemical basis for chronic and acute migraine events, and provide methods and pharmaceutical compositions related to both acute and preventive therapies for migraine events and related headaches.

Embodiments are directed to compositions and methods of treating migraine and related neurological disorders. In certain aspects, methods and compositions are for reducing cortical spreading depression and/or suppressing the neurochemical basis for chronic and acute migraine events, and provide methods and pharmaceutical compositions related to both acute and preventive therapies for migraine events and related headaches.

The present invention relates to methods of treating a disease characterised by aberrant cell proliferation (e.g., a cancer) in a human subject in need thereof. In particular, the present invention relates to treating the above conditions by administering a therapeutically effective amount of at least one agent that increases activation of a receptor of at least one type II interferon and/or type I interferon, and administering to the subject at least one agent that inhibits the Hedgehog (Hh) signalling pathway (e.g., Vismodegib). Also provided are pharmaceutical compositions, including controlled release pharmaceutical compositions, containing at least one agent that increases activation of a receptor of at least one type II interferon and/or type I interferon (e.g., a checkpoint inhibitor), an inhibitor of Hh signalling pathway, and a controlled release matrix such as a SiO.sub.2 matrix gel.

The present invention relates to methods of treating a disease characterised by aberrant cell proliferation (e.g., a cancer) in a human subject in need thereof. In particular, the present invention relates to treating the above conditions by administering a therapeutically effective amount of at least one agent that increases activation of a receptor of at least one type II interferon and/or type I interferon, and administering to the subject at least one agent that inhibits the Hedgehog (Hh) signalling pathway (e.g., Vismodegib). Also provided are pharmaceutical compositions, including controlled release pharmaceutical compositions, containing at least one agent that increases activation of a receptor of at least one type II interferon and/or type I interferon (e.g., a checkpoint inhibitor), an inhibitor of Hh signalling pathway, and a controlled release matrix such as a SiO.sub.2 matrix gel.

The present invention provides improved and/or shortened methods for expanding TILs and producing therapeutic populations of TILs, including novel methods for expanding TIL populations in a closed system that lead to improved efficacy, improved phenotype, and increased metabolic health of the TILs in a shorter time period, while allowing for reduced microbial contamination as well as decreased costs. Such TILs find use in therapeutic treatment regimens.

A composition comprising a liposome comprising a first phospholipid comprising a C.sub.14-C.sub.19:0 fatty acid and a C.sub.3-C.sub.15:0 fatty acid with a c-terminal carboxyl or a carboxaldehyde group; a second phospholipid comprising a C.sub.14-C.sub.19:0 fatty acid and a C.sub.14-C.sub.19:0 fatty acid and a sterol. The first phospholipid is preferably a phosphatidylcholine. The second phospholipid is preferably HSPC and the sterol is preferably cholesterol. In some embodiments, the molar ratio of the respective ingredients is 2-3:5-6:2-3; preferably 2:6:2; or 3:5:2, respectively. The invention also relates to the use of this composition in the targeting of M2 macrophages.