Provided herein are cell and protein therapeutics that comprise a Proteinase 3 (PR3) antibody binding domain, such as a wild type PR3 protein or mutant PR3 protein, and methods of use thereof. Also provided herein arc chimeric autoantibody receptors (CAARs) comprising an extracellular PR3 antibody binding domain. Among the provided CAARs are those in which the extracellular PR3 antibody binding domain ia a wild type or mutated PR3 protein or fragment thereof that are able to be specifically bound by an anti-PR3 antineutrophil cytoplasmic antibody (ANCA). Also provided herein are polynucleotides that encode the provided CAARs, genetically engineered cells such as T cells containing the provided CAARs, and to related methods and uses thereof in adoptive cell therapy.

The application provides bispecific chimeric antigen receptors (CARs) targeting glucose-regulated-protein 78 (GRP78) and Cluster of Differentiation 123 (CD123) or GRP78 and B7-homolog 3 (B7H3). The application further provides polynucleotides and recombinant vectors encoding the CARs, as well isolated host cells and methods for preparing isolated host cells that express the CARs. The application further provides pharmaceutical compositions comprising the CAR modified cells and methods for treating a tumor using the CAR modified cells.

The present invention relates to novel polypeptides which are derived from Arginase1. The invention also relates to polynucleotides encoding the polypeptides. The invention also relates to compositions comprising the polypeptides and polynucleotides. The invention also concerns uses of the polypeptides, polynucleotides, and compositions.

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.

Described in several example embodiments herein are engineered bifunctional receptors that can include an E3 ligase binding domain and a target binding domain operatively coupled to the E3 ligase binding domain. In some embodiments, the engineered bifunctional receptors are capable of targeted degradation of a target protein. Also described in several example embodiments herein are compositions, formulations, and cells that can include or generate the engineered bifunctional receptors and uses thereof.

Provided herein are antibodies and antigen binding portions thereof that specifically bind receptor tyrosine kinase like orphan receptor 1 (ROR1), various compositions of such antibodies or antigen binding portions thereof, recombinant nucleic acids encoding the antibodies and antigen binding portions thereof, and methods of using the antibodies or antigen-binding portions thereof in cancer therapeutics and diagnostics.

The present invention includes compositions and methods for treating AML utilizing bispecific CARs. In certain aspects, the invention includes a bispecific split CAR which binds CD13 and TIM-3 on AML cells.

The invention is directed to mutants of adenosine deaminase 2 (ADA2) that have improved catalytic activity relative to wildtype ADA2, as well as compositions comprising the mutants and methods of using the mutants to treat various conditions.

Dysfunctional or exhausted T cells arise in chronic diseases including chronic viral infections and cancer, and express high levels of co-inhibitory receptors. Therapeutic blockade of these receptors has clinical efficacy in the treatment of cancer. While co-inhibitory receptors are co-expressed, the triggers that induce them and the transcriptional regulators that drive their co-expression have not been identified. The immunoregulatory cytokine IL-27 induces a gene module in T cells that includes several known co-inhibitory receptors (Tim-3, Lag-3, and TIGIT). The present invention provides a novel immunoregulatory network and novel cell surface molecules that have an inhibitory function in the tumor microenvironment. The present invention further provides the novel discovery that the transcription factors Prdm1 and c-Maf cooperatively regulate the expression of the co-inhibitory receptor module. This critical molecular circuit underlies the expression of co-inhibitory receptors such as ILT-3 in dysfunctional T cells and identifies novel regulators of T cell dysfunction.

The present invention includes compositions and methods for treating AML utilizing bispecific CARs. In certain aspects, the invention includes a bispecific split CAR which binds CD13 and TIM-3 on AML cells.