Abstract: Cranial placodes are embryonic structures essential for sensory and endocrine organ development. The efficient derivation of cranial placodes from human pluripotent stem cells is disclosed where the timed removal of the BMP inhibitor Noggin, a component of the dual-SMAD inhibition strategy of neural induction, triggers placode induction at the expense of CNS fates. Further fate specification at the pre-placode stage enables the selective generation of placode-derived trigeminal ganglia capable of in vivo engraftment, mature lens fibers and anterior pituitary hormone-producing cells that upon transplantation produce hormones including, but not limited to, human growth hormone and adrenocortiocotropic hormone in vivo. Alternatively, anterior pituitary hormone-producing cells are generated in cell culture systems in vitro.

Abstract: The presently disclosed subject matter provides for expression cassettes that allow for expression of a globin gene or a functional portion thereof, vectors comprising thereof, and cells transduced with such expression cassettes and vectors. The presently disclosed subject matter further provides methods for treating a hemoglobinopathy in a subject comprising administering an effective amount of such transduced cells to the subject.

Abstract: Provided herein are methods of treating a nonhematopoietic malignant tumor in a patient and methods of prognosing a nonhematopoietic malignant tumor in a patient, comprising administering to the patient a therapeutically effective amount of an agent that preferentially kills or inhibits proliferation or activity of leukocytes relative to nonhematopoietic cells.

Abstract: The present disclosure provides methods for generating cortical excitatory neurons, cortical excitatory neurons generated by such methods, and composition comprising such cells. The present disclosure also provides uses of the cortical excitatory neurons and composition comprising thereof for preventing and/or treating neurodegenerative disorders.

Abstract: The present disclosure relates to the use of iron chelation to prevent and/or treat leptomeningeal metastasis. In certain embodiments, the present disclosure provides methods for the prevention and/or treatment of leptomeningeal metastasis that include the administration of an iron chelator to a subject. The present disclosure further provides kits for performing such methods.

Abstract: The present disclosure provides antibodies that specifically bind to human glucocorticoid-induced TNFR family related receptor (GITR) and compositions comprising such antibodies. In a specific aspect, the antibodies specifically bind to human GITR and modulate GITR activity, e.g., enhance, activate or induce GITR activity, utilizing such antibodies. The present disclosure also provides methods for treating disorders, such as cancer and infectious diseases, by administering an antibody that specifically binds to human GITR and modulates GITR activity e.g., enhances, activates or induces GITR activity.

Abstract: The presently disclosed subject matter provides for antigen-recognizing receptors that specifically target GD3 and cells comprising such GD3-targeted antigen-recognizing receptors. The presently disclosed subject matter further provides uses of the GD3-targeted antigen-recognizing receptors for treatment.

Abstract: Disclosed herein are methods and compositions related to the treatment, prevention, and/or amelioration of cancer in a subject in need thereof. In particular aspects, the present technology relates to the use of poxviruses, including a recombinant modified vaccinia Ankara (MVA) virus or vaccinia virus with deletion of vaccinia host-range factor C7 (MVA?C7L and VACV?C7L, respectively), alone or in combination with immune checkpoint blocking agents, as an oncolytic and immunotherapeutic composition. In some embodiments, the technology of the present disclosure relates to a MVA?C7L or VACV?C7L virus further modified to express human Fms-like tyrosine kinase 3 ligand (Flt3L).

Abstract: Described herein are systems and methods of selecting treatment parameters values for treating skin lesions. A device may establish a treatment parameter selection model using a training dataset. The training dataset may include a plurality of examples. Each example may include a sample image of an example skin lesion to which a treatment is administered using an applicator. Each example may include a first label indicating success or failure of the treatment. Each example may include a second label corresponding to treatment parameters defining the treatment. The device may identify an input image. The device may determine that the input image corresponds to a skin lesion based on visual characteristics of the input image. The device may apply the treatment parameter selection model to the input image to output a recommended treatment to apply. The device may store an association between the input image and the recommended treatment.

Abstract: The presently disclosed subject matter provides for methods and compositions for treating multiple myeloma. It relates to chimeric antigen receptors (CARs) that specifically target a G-protein coupled receptor (e.g., a G-protein coupled receptor family C group 5 member D (GPRC5D)), and immunoresponsive cells comprising such CARs. The presently disclosed CARs targeting a G-protein coupled receptor (e.g., GPRC5D) have enhanced immune-activating properties, including anti-tumor activity.

Abstract: The present disclosure relates to treating a subject comprising administering to the subject a therapy (e.g., a cell therapy, e.g., an adoptive cell therapy, e.g., a CAR-T cell therapy), wherein, prior to the administration, the subject has been preconditioned with a personalized amount of a chemotherapeutic agent. The personalized amount provides an optimal exposure to the chemotherapeutic agent.

Abstract: Described herein are multi-specific binding agents that bind A33 and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid. Also provided herein are methods of using multi-specific binding agents or compositions thereof for the detection, prevention, and/or therapeutic treatment of diseases characterized by expression of the A33 glycoprotein antigen, in particular, colorectal cancer.

Abstract: This invention provides peptides, immunogenic compositions and vaccines, and methods of treating, reducing the incidence of, and inducing immune responses to a WT1-expressing cancer, comprising heteroclitic peptides derived from the WT-1 protein.

Abstract: The present invention relates to compositions, methods, and kits for predicting a subject's response to a CAR T cell therapy, by analyzing the intestinal microbiome of the subject. The present disclosure also provides a method of detecting patients at risk for a poor response to CAR T cell therapy by measuring the level of the presently disclosed bacteria or bacterial genes in the microflora or microbiome of a patient receiving or considered for CAR T cell therapy. The present disclosure further provides therapeutic compositions and methods for treating a subject having a cancer, by improving the subject's response to a CAR T cell therapy.

Abstract: The present invention relates to methods and compositions for reducing the risk of cancer relapse in a subject who has received cancer treatment. It is based, at least in part, on the discovery that a restricted fraction of the gut microbiota, including the bacteria Streptococcus anginosus, Parvimonas micra, Acidaminococcus intestini, Eubacterium limosum, Clostridium glycyrrhizinilyticum, Desulfosporosinus lacus, Eubacterium biforme, Anaerofustis stercorihominis, Pseudoramibacter alactolyticus, Peptococcus niger, Armatimonas rosea, Saccharofermentans acetigenes, Finegoldia magna, Levyella massiliensis, Gallicola barnesae, Murdochiella asaccharolytica, and Eubacterium brachy are associated with a reduced risk of cancer relapse.

Abstract: Provided are methods and compositions for treating myeloproliferative neoplasms in patients carrying an IDH2 mutation and a JAK2 mutation.

Abstract: The invention provides antibodies, and antigen-binding fragments thereof, that specifically bind to a polypeptide, or antigenic portion thereof, wherein the polypeptide is selected from a) MUC16 ectodomain polypeptide, b) MUC16 cytoplasmic domain polypeptide, and c) MUC16 extracellular domain polypeptide that contains a cysteine loop polypeptide. The invention's antibodies and compositions containing them are useful in diagnostic and therapeutic applications for diseases in which MUC16 is overexpressed, such as cancer.

Abstract: The presently disclosed subject matter provides cells, compositions and methods for enhancing immune responses toward tumor antigens. It relates to cells comprising: an antigen-recognizing receptor (e.g., a chimeric antigen receptor, a TCR, or a TCR like fusion molecule); and a gene disruption of a CD70 locus. The gene disruption of the CD70 locus can improve the activity and/or efficiency of the cells.

Abstract: The present disclosure provides compounds, complexes, compositions, and methods for the detection of cancer. Specifically, the compounds, complexes, compositions of the present technology include pH (low) insertion peptides. Also disclosed herein are methods of using the complexes and compositions of the present technology in diagnostic imaging to detect cancer in a subject.

Abstract: Provided herein are compositions, methods, and uses involving bispecific binding molecules that specifically bind to HER2, a receptor tyrosine kinase, and to CD3, a T cell receptor, and mediate T cell cytotoxicity for managing and treating disorders, such as cancer. Also provided herein are uses and methods for managing and treating HER2-related cancers.