The invention relates to antibodies, and in particular, to antibodies exhibiting specificity for Receptor tyrosine kinase-like Orphan Receptors (ROR), and to uses thereof, for example in the treatment of cancer. The invention extends to polynucleotide and polypeptide sequences encoding the antibodies, and therapeutic uses thereof, and to diagnostic kits comprising these molecules. The invention also extends to antibody-drug conjugates and to uses thereof in therapy.

Methods of non-invasively imaging a subject using two or more antigen-binding constructs that selectively bind to immune cell markers are described.

Multispecific antibodies (e.g., bispecific antibodies) that bind to HIV gp120 and CD3 are disclosed. Also disclosed are methods of using such antibodies to treat or prevent HIV infection.

Compositions and methods for transient immunodepletion of specific subsets of a subject's immune cells are disclosed. The methods generally include administering to the subject an effective amount of a radiolabeled antibody against CD19, CD20, CD33, CD38, CD45RA, CD52, or a combination thereof. The effective amount of the radiolabeled antibody depletes at least 50% of the targeted immune cells, and less than 20% of the subject's stem cells. When used alone, these methods may target lymphomas, leukemias, and myelomas, and/or may additionally allow repopulation of non-autoreactive immune cells in patients with an autoimmune disease. When these methods precede certain cell-based therapies, such as adoptive cell therapy and/or hematopoietic stem cell therapy, the methods are able to enhance the outcome of the cell-based therapies while minimizing adverse effects.

A multiple antigen-binding molecule fusion molecule containing a multiple antigen-binding molecule (α) having an immune cell antigen-binding region and a cancer antigen-binding region, a cancer tissue-specific protease-cleavable linker (β), and a masking molecule (γ) containing a polypeptide having the amino acid sequence QDGNE, in which the multiple antigen-binding molecule (α) and the masking molecule (γ) are linked via the cancer tissue-specific protease-cleavable linker (β).

A multiple antigen-binding molecule fusion molecule containing a multiple antigen-binding molecule (α) having an immune cell antigen-binding region and a cancer antigen-binding region, a cancer tissue-specific protease-cleavable linker (β), and a masking molecule (γ) containing a polypeptide having the amino acid sequence QDGNE (SEQ ID NO: 15), in which the multiple antigen-binding molecule (α) and the masking molecule (γ) are linked via the cancer tissue-specific protease-cleavable linker (β).

Provided herein are methods of treating cancer using bispecific antigen-binding molecules that bind to prostate-specific membrane antigen (PSMA) and CD3. According to certain embodiments, the antibodies useful herein bind human PSMA with high affinity and bind CD3 to induce human T cell proliferation. According to certain embodiments, bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD3, and a second antigen-binding molecule that specifically binds human PSMA are particularly useful herein. In certain embodiments, the bispecific antigen-binding molecules in combination with an anti-4-1BB agonist are capable of inhibiting the growth of prostate tumors expressing PSMA. The bispecific antigen-binding molecules in combination with an anti-4-1BB agonist are useful for the treatment of diseases and disorders in which an upregulated or induced targeted immune response is desired and/or therapeutically beneficial, for example, in the treatment of various cancers.

Provided herein are method of treating cancer using bispecific antigen-binding molecules that bind to Mucin 16 (MUC16) and CD3. According to certain embodiments, the antibodies useful herein bind human MUC16 with high affinity and bind CD3 to induce human T cell proliferation. According to certain embodiments, bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD3, and a second antigen-binding molecule that specifically binds human MUC16 are particularly useful herein. In certain embodiments, the bispecific antigen-binding molecules in combination with an anti-4-1BB agonist are capable of inhibiting the growth of tumors expressing MUC16, for example, ovarian tumors. The bispecific antigen-binding molecules in combination with an anti-4-1BB agonist are useful for the treatment of diseases and disorders in which an upregulated or induced targeted immune response is desired and/or therapeutically beneficial, for example, in the treatment of various cancers.

Multispecific antibodies (e.g., bispecific antibodies) that bind to HIV gp120 and CD3 are disclosed. Also disclosed are methods of using such antibodies to treat or prevent HIV infection.

The present invention relates to a novel feeder cell and a method for growing gamma delta T cells using the same. More specifically, a large amount of gamma delta T cells may be grown in vitro with high purity and without simulation of a T cell receptor by using a feeder cell into which costimulatory molecules are introduced and a low concentration of IL-2, differentiation into central memory cells may be possible when stimulated, activity by the feeder cell, and cytolytic against tumour cells is provided.