A conjugate of formula I:
L-(D.sup.L).sub.P  (1) wherein L is a Ligand unit, D.sup.L is a Drug Linker unit of formula II: ##STR00001## wherein either: (a) R.sup.10 and R.sup.11 form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound; or (b) R.sup.11 is OH, and R.sup.10 is: ##STR00002## p is an integer of from 1 to 20.

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 present invention provides methods of testing anti-STn antibodies for their ability target cancer stem cells by isolating cancer stem cells from cultures, contacting them with anti-STn antibodies being tested, and measuring resulting cell viability.

Compositions and methods for treating ovarian cancer are provided. Methods include combined treatment with chemotherapeutic agents and anti-STn antibodies. Chemotherapy resistant ovarian cancer cells may be reduced. Chemotherapy resistant ovarian cancer cells may include cancer stem cells.

The present disclosure relates generally to cysteine engineered antibody-drug conjugates comprising peptide-containing linkers and to methods of using these conjugates as therapeutics and/or diagnostics.

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.

Provided herein are methods for the treatment of cancers with antibody drug conjugates (ADC) that bind to 191P4D12 proteins. Also provided herein are methods for the treatment of urothelial cancer using an antibody drug conjugate (ADC) that binds 191P4D12. Additionally provided herein are methods for the treatment of solid tumors using an antibody drug conjugate (ADC) that binds 191P4DI2.

The present invention relates to new antibody-drug conjugates (ADCs) targeting ROR1, active metabolites of such ADCs, methods for preparation of such ADCs, uses for such ADCs in treatment and/or prevention of illnesses, and uses for such ADCs in production of drugs for treatment and/or prevention of diseases, more specifically diseases associated with over-expression of ROR1, for example cancer. More specifically, the present invention relates to an antibody-drug conjugate comprising an antibody that binds to ROR1 or an antigen-binding fragment thereof, and a pharmaceutical composition comprising the same.

Methods are provided for identifying and selecting antibodies that are internalized into cells via the macropinocytosis pathway. Additionally antibodies that are internalized via this pathway are provided as well as immunoconjugates comprising such antibodies.

The present disclosure provides methods comprising administering to the individual an effective amount of an agent that decreases or inhibits TIGIT expression and/or activity and an anti-cancer agent and/or an anti-cancer therapy. Further provided are kits comprising an anti-cancer agent, an agent that decreases or inhibits TIGIT expression and/or activity, or both, as well as instructions for use thereof.