The present invention concerns improved methods and compositions for preparing SN-38 conjugates of proteins or peptides, preferably immunoconjugates of antibodies or antigen-binding antibody fragments. More preferably, the SN-38 is attached to the antibody or antibody fragment using a CL2A linker, with 1-12, more preferably 6-8, alternatively 1-5 SN-38 moieties per antibody or antibody fragment. Most preferably, the immunoconjugate is prepared in large scale batches, with various modifications to the reaction scheme disclosed herein to optimize yield and recovery in large scale. Other embodiments concern optimized dosages and/or schedules of administration of immunoconjugate to maximize efficacy for disease treatment and minimize side effects of administration.

Products, compositions, systems, and methods for modifying a target structure which mediates or is associated with a biological activity, including treatment of conditions, disorders, or diseases mediated by or associated with a target structure, such as a virus, cell, subcellular structure or extracellular structure. The methods may be performed in situ in a non-invasive manner by application of an initiation energy to a subject thus producing an effect on or change to the target structure directly or via a modulation agent. The methods may further be performed by application of an initiation energy to a subject in situ to activate a pharmaceutical agent directly or via an energy modulation agent, optionally in the presence of one or more plasmonics active agents, thus producing an effect on or change to the target structure. Kits containing products or compositions formulated or configured and systems for use in practicing these methods.

The present disclosure provides methods of treating cancer in a patient comprising administering a combination of a low dose radiotherapy and an immune checkpoint inhibitor therapy. The patient may be further administered a cell therapy, such as chimeric antigen receptor T-cell therapy or chimeric antigen receptor NK-cell therapy. The low dose radiation modulates the tumor microenvironment of solid tumors to allow better efficacy, activation, and infiltration of the anti-tumor effector immune cells.

The present invention provides methods for treating, reducing the severity, or inhibiting the growth of cancer (e.g., skin cancer). The methods of the present invention comprise administering to a subject in need thereof a therapeutically effective amount of a programmed death 1 (PD-1) antagonist (e.g., an anti-PD-1 antibody). In certain embodiments, the skin cancer is cutaneous squamous cell carcinoma or basal cell carcinoma.

The present disclosure relates to the field of nanomedicine, in particular for treating cancers. The present disclosure more specifically provides new methods of treating undesirable M2-polarized macrophages and/or inducing M1 macrophage polarization in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of nanoparticles containing metallic elements.

The present disclosure offers therapeutic solutions to cancer patients up to now considered as unable to undergo a standard-of-care treatment involving radiotherapy or at high risk to undergo a standard-of-care treatment involving radiotherapy. The disclosure relates to nanoparticles and/or aggregates of nanoparticles for use in the treatment of cancer in such a patient, wherein the nanoparticles and/or aggregates of nanoparticles preferably comprise more than 30% by weight of at least one chemical element having an atomic number (Z) between 20 and 83. The disclosed treatments involve a step of administering the nanoparticles and/or aggregates of nanoparticles to the patient, and a step of exposing the patient to a total dose of ionizing radiations that is equal to or less than 85% of the total dose delivered in the standard-of-care treatment. The present description also discloses new compositions comprising such nanoparticles and/or aggregates of nanoparticles as well as uses thereof.

Residual, refractory or relapsed cancer is treated by immunostimulation in the presence of allogeneic immune effector cells, optimally in combination with radiation therapy. The methods of the disclosure induce a systemic allogeneic anti-tumor immune response that results in tumor regression in untreated sites of disease, i.e. non-injected, non-irradiated, etc.

A fluorocarbon emulsion in water for use in fractionated radiotherapy and chemotherapy, wherein said fluorocarbon comprises between 4 and 8 carbon atoms.

A method for treating a tumor, comprising identifying a tumor as a pancreatic cancer tumor and implanting in the tumor identified as a pancreatic cancer tumor, as least one diffusing alpha-emitter radiation therapy (DaRT) source with a suitable radon release rate and for a given duration, such that the source provides during the given duration a cumulated activity of released radon between 5.6 Mega becquerel (MBq) hour and 9.5 MBq hour, per centimeter length.

A method for treating a tumor, comprising identifying a tumor as a glioblastoma tumor and implanting in the tumor identified as a glioblastoma tumor, as least one diffusing alpha-emitter radiation therapy (DaRT) source with a suitable radon release rate and for a given duration, such that the source provides during the given duration a cumulated activity of released radon between 3.7 Mega becquerel (MBq) hour and 8.8 MBq hour, per centimeter length.