Methods and compositions related to the engineering of a protein with MTA/ADO-degrading enzyme activity are described. For example, in certain aspects there may be disclosed an MTase capable of degrading MTA/ADO. Furthermore, certain aspects of the invention provide compositions and methods for the treatment of cancer or SCID with an MTase using the disclosed proteins or nucleic acids.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits activity of a disease allele associated with muscle disease. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

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.

This disclosure provides compositions and methods for delivering a viral composition to cells, e.g., for cell surface receptor-mediated uptake, and enhanced viral transduction. Viral transduction can be achieved via a bifunctional bridging composition that includes a moiety that binds to a cell surface receptor ligand and a linked bridging moiety that binds to a viral composition. Also provided are modified viral compositions comprising a bridging composition specifically bound via its bridging moiety to the viral composition. Modified viral compositions and methods for reducing levels or titers of neutralizing antibodies in a subject in need of viral therapy, e.g., gene therapy, are provided. In some embodiments, the modified viral composition includes empty viral particles that bind and internalize neutralizing autoantibodies. Modified viral compositions including empty viral particles can be administered prior to viral therapy. Also provided are pharmaceutical compositions and kits including a bifunctional bridging composition and/or modified viral compositions.

The invention is directed to a bispecific chimeric antigen receptor, comprising: (a) at least two antigen-specific targeting regions; (b) an extracellular spacer domain; (c) a transmembrane domain; (d) at least one co-stimulatory domain; and (e) an intracellular signaling domain, wherein each antigen-specific targeting region comprises an antigen-specific single chain Fv (scFv) fragment, and binds a different antigen, and wherein the bispecific chimeric antigen receptor is co-expressed with a therapeutic control. The invention also provides methods and uses of the bispecific chimeric antigen receptors.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits expression or activity of DUX4. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

The invention provides anti-Jagged antibodies and methods of using the same.

The current invention describes a conjugate of a targeting moiety linked to a drug via a molecule having high affinity for the targeting moiety at physiological pH such that the drug releases at low pH from the targeting moiety.

This disclosure relates to anti-cancer antibodies and methods of treatment, detection, and diagnosis using the same.

The disclosure relates generally to polyglutamated antifolates, formulations containing liposomes filled with the polyglutamated antifolates, methods of making the polyglutamated antifolates and liposome containing formulations, and methods of using the polyglutamated antifolates and liposome containing formulations to treat hyerproliferative disorders (e.g., cancer) and disorders of the immune system (e.g., an autoimmune disease such as rheumatoid arthritis).