Described are peptides and peptide conjugates comprising CN binding motifs (CNBM) which inhibit the CN-NFAT interaction. In some embodiments, the peptides comprise: (i) CNBM; (ii) a hydrophobic, non-peptidic moiety (RH) which interacts with the hydrophobic pocket on a CN protein; (iii) a sequence -AAU1-AAU2-AAU3-AAU4-AAU5-AAU6-, wherein each of AAU2, AAU3, AAU4, AAU5, and AAU6, is, independently, optional, and each of AAU1, AAU2, AAU3, AAU4, AAU5, and AAU6 when present is independently an amino acid as defined herein; or (iv) combinations thereof. In some embodiments, RH is conjugated to the N- or C-terminus of the CNBM. In some embodiments, the sequence -AAU1-AAU2-AAU3-AAU4-AAU5-AAU6- is conjugated to the N- or C terminus of the CNBM. In some embodiments, the peptides comprise: CNBM and RH. In some embodiments. In some embodiments, the peptides comprise: CNBM and AAU1-AAU2-AAU3-AAU4-AAU5-AAU6-. In some embodiments, the peptides of the disclosure CNBM and RH.

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.

The present invention relates to a method of using a receptor (e.g., chimeric antigen receptor—CAR) that activates an immune response upon binding a cancer cell ligand in conjunction with a target-binding molecule that targets a protein or molecule CI for removal or neutralization to generate enhanced anti-cancer immune cells. The present invention also relates to engineered immune cells having enhanced therapeutic efficacy and uses thereof.

Disclosed are compositions comprising an IL-2:anti-IL-2 antibody (Ab) complex (IL-2C) and methods of using said N compositions for the treatment of microbial infections, autoimmune diseases, autoinflammatory diseases, or cancers as well the treatment of inflammatory conditions or reduction in inflammation caused by said microbial infections, autoimmune diseases, autoinflammatory diseases, or cancers.

The present disclosure relates to constructs, such as antibody molecules comprising a binding domain specific to CD45, said binding domain comprising SEQ ID NO: 1, 2, 3 and/or SEQ ID NO: 4, 5 and 6. The disclosure also extends to pharmaceutical compositions comprising said constructs and use of the constructs/compositions in treatment.

Provided herein are PD-1 antigen-binding proteins and related nucleic acids, vectors, host cells, kits and pharmaceutical compositions. Methods of making PD-1 antigen-binding proteins and methods of treating a subject are further provided.

Compositions and methods useful for the treatment of hemoglobinopathies and hematological diseases are disclosed herein. The compositions include an actinium-225 labeled anti-CD45 antibody (BC8) formulated as a single patient dose that is wholly deliverable to a patient in a single dose. The actinium-225 labeled anti-CD45 may be administered alone or in combination with additional therapeutic agents, such as other immunotherapeutics or a radiosensitizing agent, or additional therapeutic interventions, such as bone marrow transplant or adoptive cell therapies.

Disclosed herein are reagents, compositions and methods for isolating and detecting rare cells such as circulating multiple myeloma cells as well as method of evaluating and treating patients suspected of having diseases of abnormal plasma cells, such as multiple myeloma.

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 relates to a method of using a receptor (e.g., chimeric antigen receptor—CAR) that activates an immune response upon binding a cancer cell ligand in conjunction with a target-binding molecule that targets a protein or molecule for removal or neutralization to generate enhanced anti-cancer immune cells. The present invention also relates to engineered immune cells having enhanced therapeutic efficacy and uses thereof.