This disclosure relates to anti-human CD154 antibodies with modified effector function. This disclosure also relates to the use of these anti-human CD154 antibodies in treating conditions associated with CD154 activation, such as transplant rejection, inflammatory conditions and disease, dysfunctional immune responses associated with viral infections and diseases, autoimmune conditions and disease, allergic conditions, atherosclerotic conditions, or neurodegenerative conditions and diseases. It also relates to the use of these anti-human CD154 antibodies in inducing central tolerance and hematopoietic chimerism in transplant patients.

Described are tetravalent, bispecific EGFR/CD16A antigen-binding proteins for engaging NK-cells towards EGFR-positive cells. EGFR/CD16A antigen-binding proteins with different pharmacokinetic (PK) properties are described. Further described is the use of bispecific EGFR/CD16A antigen-binding proteins for the treatment of an EGFR-positive malignancy, such as EGFR-positive tumors.

Provided are a chimeric antigen receptor capable of targeting B7-H3, a nucleic acid molecule encoding the chimeric antigen receptor, a nucleic acid construct comprising the nucleic acid molecule, an immune effector cell expressing the chimeric antigen receptor, and use thereof. The chimeric antigen receptor comprises an anti-B7-H3 binding domain, a hinge region, a transmembrane domain and a signal transduction domain. Further provided are a composition and a method for diagnosing, treating or preventing tumors that express B7-H3.

The present disclosure provides novel dominant negative Fas polypeptides comprising a first modification in the cytoplasmic domain and a second modification in the N-terminal region of human Fas. The present disclosure also provides cells comprising such novel dominant negative Fas polypeptides and an antigen-recognizing receptor (e.g., a chimeric antigen receptor (CAR) or a T cell receptor (TCR)). Also provided are uses of the cells for treatment, e.g., for treating tumors and pathogen infections.

The presently disclosed subject matter provides for chimeric receptors that target ADGRE2 and chimeric receptors that target CLEC12A. The presently disclosed subject matter also provides for cells comprising the ADGRE2-targeted chimeric receptors, cells comprising the CLEC12A-targeted chimeric receptors, and cells comprising the ADGRE2-targeted chimeric receptors and the CLEC12A-targeted chimeric receptors. The presently disclosed subject matter further provides uses of such cells for treating tumors, e.g., AML.

The present disclosure provides methods of treating cancer in a patient, comprising administering to the patient a chemotherapeutic agent, an immunomodulatory agent, and an antisense compound targeted to STAT3. Also provided herein are compositions and kits for performing the methods provided herein. In preferred embodiments, the chemotherapeutic agent is cisplatin, the antisense compound targeted to STAT3 is AZD9150, and the immunomodulatory agent is MEDI4736.

The disclosure provides CARs (CARs) that specifically bind to CD70. The disclosure further relates to engineered immune cells comprising such CARs, CAR-encoding nucleic acids, and methods of making such CARs, engineered immune cells, and nucleic acids. The disclosure further relates to therapeutic methods for use of these CARs and engineered immune cells comprising these CARs for the treatment of a condition associated with malignant cells expressing CD70 (e.g., cancer).

In one embodiment, the present disclosure provides an engineered cell having a first chimeric antigen receptor polypeptide including a first antigen recognition domain, a first signal peptide, a first hinge region, a first transmembrane domain, a first co-stimulatory domain, and a first signaling domain; and a second chimeric antigen receptor polypeptide including a second antigen recognition domain, a second signal peptide, a second hinge region, a second transmembrane domain, a second co-stimulatory domain, and a second signaling domain; wherein the first antigen recognition domain is different than the second antigen recognition domain.

The present invention encompasses methods of cancer immunotherapy, and particularly methods of allogeneic cellular immunotherapy, using particular lymphodepletion regimens in combination with particular populations of chimeric antigen receptor T cells expressing anti CD19 CAR PBCAR0191, anti CD20 CAR PBCAR20A or anti BCMA CAR PBCAR269A.

The presently disclosed subject matter provides methods for treating neoplasia using cells comprising an antigen-recognizing receptor (e.g., a chimeric antigen receptor (CAR)) that specifically targets CD127.