Provided herein are, inter alia, antibody compounds comprising an anti-immune cell antibody (e.g., anti-CD3 antibody) covalently bound to a CS-1-binding antibody; immune cells bound to compounds comprising an anti-immune cell antibody (e.g., anti-CD3 antibody) covalently bound to a CS-1-binding antibody; humanized OKT3 antibodies; pharmaceutical compositions; and methods for treating cancer, such as multiple myeloma.

Provided herein are antibodies and antigen-binding portions thereof that bind to tumor endothelial marker 1 (TEM1), as well as methods of using the disclosed antibodies and antigen-binding portions thereof, including methods of treating cancer, reducing tumor growth, reducing tumor metastasis, and/or reducing tumor-associated fibrosis in a subject in need thereof.

Provided herein are compositions with an augmented capacity to mediate ADCC. These compositions include chimeric NK cellscalled Nukes (NK Enhancement Strategy) that express CD64 Fc receptor from an exogenous nucleic acid molecule, the NK cells having antibodies bound thereto. Methods of using these cells for treatment of HIV, cancer, SARS-COV-2, and other diseases are provided.

Provided herein are compositions with an augmented capacity to mediate ADCC. These compositions include chimeric NK cellscalled Nukes (NK Enhancement Strategy) that express CD64 Fc receptor from an exogenous nucleic acid molecule, the NK cells having antibodies bound thereto. Methods of using these cells for treatment of HIV, cancer, SARS-COV-2, and other diseases are provided.

CD38 is also expressed in a variety of malignant hematological diseases, including multiple myeloma. In the present invention, the inventors have generated a new antibody against CD38 that could be suitable for producing bispecific antibodies as well as CAR-T cells. In particular, the inventors report the development of Bi38-3, a new bispecific T cell engager that targeted CD38 on MM cells and recruited cytotoxic T cells through the CD3. Bi38-3 lacked the Fc region of natural mAb, which contributes to resistance processes, but triggered T cells to proliferate, release cytokine and lyse CD38 positive MM cells in vitro. Similarly, Bi38-3 induced autologous T cells to eliminate tumor plasma cells isolated from MM patients both at diagnosis and at relapse. The cytotoxicity triggered by Bi38-3 was restricted to cells expressing high levels of CD38 and preserved the integrity of T, B and NK lymphocytes in vitro. Importantly, Bi38-3 rapidly reduced tumor cells in an MM1.S xenograft mouse model of human MM. Taken together, the results show that the antibody of the present invention is an effective reagent to specifically eliminate CD38 positive malignant cells without significantly affecting CD38 lowly expressing cells and represents a promising novel immunotherapeutic tool for the treatment of malignant hematological diseases, and especially multiple myeloma.

CD38 is also expressed in a variety of malignant hematological diseases, including multiple myeloma. In the present invention, the inventors have generated a new antibody against CD38 that could be suitable for producing bispecific antibodies as well as CAR-T cells. In particular, the inventors report the development of Bi38-3, a new bispecific T cell engager that targeted CD38 on MM cells and recruited cytotoxic T cells through the CD3. Bi38-3 lacked the Fc region of natural mAb, which contributes to resistance processes, but triggered T cells to proliferate, release cytokine and lyse CD38 positive MM cells in vitro. Similarly, Bi38-3 induced autologous T cells to eliminate tumor plasma cells isolated from MM patients both at diagnosis and at relapse. The cytotoxicity triggered by Bi38-3 was restricted to cells expressing high levels of CD38 and preserved the integrity of T, B and NK lymphocytes in vitro. Importantly, Bi38-3 rapidly reduced tumor cells in an MM1.S xenograft mouse model of human MM. Taken together, the results show that the antibody of the present invention is an effective reagent to specifically eliminate CD38 positive malignant cells without significantly affecting CD38 lowly expressing cells and represents a promising novel immunotherapeutic tool for the treatment of malignant hematological diseases, and especially multiple myeloma.

Provided is a method of treating cancer in an individual by administering to the individual modified cells that express a chimeric antigen receptor (CAR) that contain a TIGIT extracellular domain that can bind to poliovirus receptor (PVR), a CD28 segment, and a CD3 segment. The modified cells may co-express and secrete a Bi-specific T cell engager (BiTE). The BiTE includes a segment that can specifically bind to human Folate Receptor alpha (FR) and a segment that that can specifically bind to a human CD3 segment. Modified cells that express the CAR, and may also express and secrete the BiTE, and polynucleotides encoding the CAR and the BiTE, are also provided.

Provided is a method of treating cancer in an individual by administering to the individual modified cells that express a chimeric antigen receptor (CAR) that contain a TIGIT extracellular domain that can bind to poliovirus receptor (PVR), a CD28 segment, and a CD3 segment. The modified cells may co-express and secrete a Bi-specific T cell engager (BiTE). The BiTE includes a segment that can specifically bind to human Folate Receptor alpha (FR) and a segment that that can specifically bind to a human CD3 segment. Modified cells that express the CAR, and may also express and secrete the BiTE, and polynucleotides encoding the CAR and the BiTE, are also provided.

Embodiments of the disclosure concern methods and compositions related to targeted cancer therapy directed to a particular terminal deoxynucleotidyl transferase peptide associated with HLA-A02. In specific embodiments, cellular therapy employs cells encoding a chimeric T-cell receptor that targets the peptide and optionally also a bi-specific T-cell engager that targets the same peptide. In particular embodiments, one or both are used to treat a hematological malignancy.

Embodiments of the disclosure concern methods and compositions related to targeted cancer therapy directed to a particular terminal deoxynucleotidyl transferase peptide associated with HLA-A02. In specific embodiments, cellular therapy employs cells encoding a chimeric T-cell receptor that targets the peptide and optionally also a bi-specific T-cell engager that targets the same peptide. In particular embodiments, one or both are used to treat a hematological malignancy.