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.

The invention describes anti-cancer therapies comprising using an MDM2 inhibitor in combination with a PD-1 antagonist and a LAG-3 antagonist, each as described herein.

The invention provides an anti-PD-1 antibody comprising the complementary determining regions (CDRs) of pembrolizumab in combination with an antibody-drug conjugate that binds to tissue factor (TF) comprising monomethyl auristatin E and the CDRs of tisotumab (e.g., tisotumab vedotin) and their use in methods of treating cancer, such as breast cancer and cervical cancer. The invention also provides compositions and kits comprising the anti-PD-1 antibody comprising the CDRs of pembrolizumab and the antibody-drug conjugate that binds to TF comprising monomethyl auristatin E and the CDRs of tisotumab (e.g., tisotumab vedotin) for use in treating cancer, such as breast cancer and cervical cancer.

Disclosed herein are methods of treating HNSCC that comprises administration of a HER3 blocker and an immune checkpoint modulator. In some embodiments, also disclosed herein is a method of modulating activity level of the PI3K/AKT/mTOR pathway in a HNSCC cell to modulate proliferation or sensitization of the cancer cell to a treatment therapy.

IL33 antagonists alone or in combination with IL-4R antagonists can be used to treat or inhibit eosinophilic asthma, eosinophilic COPD, eosinophilic ACOS, and nasal polyps in a subject having one or more risk alleles in the intronic IL1RL1 variant rs1420101, in the IL33 variant rs1342326, in both, or in variants in linkage disequilibrium thereof.

The present invention generally pertains to methods of quantitating therapeutic proteins co-administered to a subject using LC-MRM-MS. In particular, the present invention pertains to the use of dual enzymatic digestion to generate unique surrogate peptides allowing for the accurate quantitation of co-administered therapeutic proteins using LC-MRM-MS.

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.

Genetically programmed microorganisms, such as bacteria or virus, pharmaceutical compositions thereof, and methods of modulating and treating cancers are disclosed.

Combination therapy of a cancer with a multi-specific binding protein that bind a tumor associated antigen, the NKG2D receptor, and CD16, in combination with a second anti-cancer agent are described. Also described are pharmaceutical compositions of the multi-specific binding protein, and therapeutic methods useful for the treatment of cancer in combination with a second anti-cancer agent.

The present invention is directed to dosing regimens for administering a humanized anti-B7-H3 antibody conjugated to at least one duocarmycin moiety (a “B7-H3-ADC”) for the treatment of cancer, particularly a cancer associated with expression of B7-H3. The invention particularly concerns the use of such B7-H3-ADC optionally in combination with a PD-1 binding molecule for the treatment of cancer. The invention particularly concerns the use of such B7-H3-ADC and an anti-PD-1 antibody or a PD-1 X LAG-3 bispecific molecule. The invention is directed to the use of such molecules, and to the use of pharmaceutical compositions and pharmaceutical kits that contain such molecules and that facilitate the use of such dosing regimens in the treatment of cancer.