The present disclosure describes certain technologies for administering large agent(s) (e.g., biologically active large agents such as biologic therapeutics including, for instance, botulinum toxin) to subjects, including technologies that achieve unexpected results such as, for example, delayed peak effect and/or extended duration of response.

This disclosure relates to methods for improving the therapeutic index of a chemotherapeutic drug in the treatment of patients afflicted with cancer, by reducing chemotherapy-related toxicity to a level that allows the chemotherapeutic drug to be used in humans.

Methods, compositions and uses are provided for bispecific antibodies comprising one or more unnatural amino acids. The bispecific antibodies may bind to two or more different receptors, co-receptors, antigens, or cell markers on one or more cells. The bispecific antibodies may be used to treat a disease or condition (e.g., cancer, autoimmune disease, pathogenic infection, inflammatory disease). The bispecific antibodies may be used to modulate (e.g., stimulate or suppress) an immune response.

The present invention provides PD-1 monoclonal antibodies, particularly human monoclonal antibodies of PD-1, which specifically bind to PD-1 with high affinity and comprise a heavy chain and a light chain. The present invention further provides nucleic acid sequence encoding the antibodies of the invention, cloning or expression vectors, host cells and methods for expressing or isolating the antibodies. Immunoconjugates, therapeutic compositions comprising the antibodies of the invention are also provided. The invention also provides methods for treating various cancers with anti-PD-1 antibodies.

Provided herein are methods of depleting T cells for therapeutic uses, including administration of anti-CD2 or anti-CD5 antibody drugs conjugates (ADCs) for treatment. Provided are anti-CD2 ADCs or anti-CD5 ADCs for use as agents to treat a stem cell disorder, cancer, or autoimmune disease, among other hematological and proliferative diseases. The compositions and methods described can be used to deplete populations of CD2+ or CD5+ cells, such as CD2+ or CD5+ cancer cells or CD2+ or CD5+ immune cells, and can also be used to prepare a patient for hematopoietic stem cell transplantation or solid organ transplantation.

The present disclosure relates to antibody-drug conjugates comprising ALK5 inhibitors and their uses.

Provided are ionizable cationic lipids and lipid nanoparticles for the delivery of nucleic acids to cells (e.g., immune cells), and methods of making and using such lipids and targeted lipid nanoparticles.

The present invention includes compositions and methods for treating T cell lymphomas and leukemias. In certain aspects, the compositions and methods include CAR T cells targeting CD2, CD5, or CD7 and modified cells wherein CD2, CD5, or CD7 has been knocked-out.

The present invention relates to the application of a three-dimensional (3D) bioreactor for T-cell expansion for immunotherapy.

The present disclosure is directed, in some embodiments, to methods and compositions of comprising a cell having a non-internalizing receptor, and a nanoparticle surface-modified with a ligand that binds to the non-internalizing receptor.