Disclosed are agents for treating or preventing cancers. More particularly, the present invention discloses therapeutic combinations comprising antagonists of receptor of NF-κB (RANK) ligand and immune checkpoint molecules in methods and compositions for treating or inhibiting the development, progression or recurrence of cancers, including metastatic cancers.

Expression of lambda antibody light chain with non-native leader sequence, wherein light chain is sequence-engineered to restore native N terminus. Immunoglobulin lambda variable domain sequence comprising N terminal deletion for expression with non-native N terminal signal peptide.

Provided are CD3 binding molecules that specifically bind to CD3, for example monospecific binding molecules that specifically bind to CD3 and multispecific binding molecules (MBMs) that specifically bind to CD3 and a tumor-associated antigen, conjugates comprising the CD3 binding molecules, and pharmaceutical compositions comprising the CD3 binding molecules and conjugates. Provided are methods of using the CD3 binding molecules, conjugates, and pharmaceutical compositions to activate T cells in a subject, for example a subject having a cancer or autoimmune disease. Provided are recombinant host cells engineered to express the CD3 binding molecules and methods of producing the CD3 binding molecules by culturing the host cells under conditions in which the CD3 binding molecules are expressed.

The present invention relates to combination therapies useful for the treatment of cancer. In particular, the invention relates to the combined use of a PD-1 inhibitor, a TGFβ inhibitor, an ATM inhibitor and radiation to treat cancer.

Methods and compositions for treating cancer in a subject in need thereof. The method includes administering to the subject an effective amount of a composition comprising Tumor-Targeting Effectors (TITE) derived from a culture comprising a bispecific antibody armed activated T cell (BAT) and a cancer cell, to thereby treat cancer in the subject.

Provided herein are anti-CD 19 antibodies and multi-specific binding proteins that bind CD 19, CD3, and serum albumin. Also provided are pharmaceutical compositions comprising these antibodies or multi-specific binding proteins, expression vectors and host cells for making these antibodies or multi-specific binding proteins, and methods of use of these antibodies or multi-specific binding proteins in treating cancers.

The present disclosure provides isolated monoclonal antibodies or antigen-binding portions thereof that specifically bind to CD47 preferably human CD47 with high affinity, and can enhance tumor-targeting immune response by therapeutically boosting the phagocytic function of macrophage for cancer treatment. The disclosure also provides antibodies that are chimeric, humanized, bispecific, derivatized, single chain antibodies or portions of fusion proteins. Nucleic acid molecules encoding the antibodies of the disclosed invention and hybridoma are also provided. Pharmaceutical compositions comprising the antibodies of the disclosed invention are also provided. This disclosure also provides methods for regulating innate immune responses, as well as methods for treating cancer using an anti-CD47 antagonist antibody of the disclosed invention.

Provided are anti-TIGIT antibodies that bind to “T cell immunoreceptor with Ig and ITIM domains (TIGIT)”, including multispecific anti-TIGIT antibodies with binding specificity for TIGIT and one or more additional antigen, and methods of using the same. In certain embodiments, the anti-TIGIT antibodies comprises a single domain antibody that binds to TIGIT. In certain embodiments, the one or more additional antigen comprises Programmed cell death ligand 1 (PDL1).

Methods and systems to reduce neurotoxicity associated with the treatment of CD19.sup.+ B-cell hyperproliferative disorders are disclosed. Neurotoxicity is reduced by the use of agents that protect CD19.sup.+ neurovascular pericytes and/or CD19.sup.+ vSMCs from attack by CD19-targeted therapy, and by modification of CD19-targeted therapy to avoid CD19.sup.+ pericytes and/or CD19.sup.+ vSMCs.

This disclosure relates to modified immunoglobulins.