The present disclosure generally relates to, among other things, a new class of receptors engineered to modulate transcriptional regulation in a ligand-dependent manner Particularly, the new receptors, even though derived from Notch and Robo, do not require the Notch or Robo regulatory regions previously believed to be necessary for the functioning of the receptors. The disclosure also provides compositions and methods useful for producing such receptors, nucleic acids encoding same, host cells genetically modified with the nucleic acids, as well as methods for modulating an activity of a cell and/or for the treatment of various health conditions such as diseases (e.g., cancers).

The present disclosure provides methods and compositions related to Natural Killer T cells that are engineered to knock down the expression of one or more endogenous major histocompatibility complex (MHC) gene. The present disclosure also provides engineered CAR NKT cells that resist rejection by allogeneic immune cells both in vitro and in vivo.

The present invention provides a novel PSMA binding antibody termed 10B3 and pharmaceutical and diagnostic uses of the antibody 10B3. The PSMA antibody 10B3 does not cross-compete with the state of the art PMSA binding antibody J591 and has a reduced induction of antigen shift compared to J591 and a unique reactivity with squamous cell carcinoma (SCC) cells of different origin.

The present invention relates to preparations and methods for treating a GD2 positive cancer by administering a preparation comprising a chimeric or humanized anti-GD2 antibody to a patient, wherein the patient is not concomitantly treated with Interleukin-2 (IL-2 wherein a GD2 positive cancer is treated in the patient. Furthermore, the invention relates to preparations and methods for the treatment of a GD2 positive cancer in a patient, wherein a preparation comprising an anti-GD2 antibody is administered to the patient as a continuous infusion, without concomitantly administering IL-2. The present invention further relates to preparations and methods for the treatment of a GD2 positive cancer in a patient, wherein the one or more anti-GD2 antibody treatment periods is/are preceded, accompanied, and/or followed by one or more treatment periods with a retinoid.

The present invention relates generally to the identification and isolation of human otic progenitor cells. More specifically, the present invention relates to a method of using cell markers to identify and isolate human otic progenitor cells from a mixed population of cells, methods of enrichment and production of human otic progenitor cells, and associated kits for use in identification and/or isolation of human otic progenitor cells, wherein the cell markers are selected from SSEA1 (CD15), disialoganglioside GD3, TRA-2-49 (liver/bone/kidney alkaline phosphatase), SSEA4, ganglioside GD2 and CD141.

The disclosed method of treating a malignant solid tumor in a subject includes the steps of administering to the subject an immunomodulatory dose of a radioactive phospholipid ether metal chelate, a radiohalogenated phospholipid ether, or other targeted radiotherapy (TRT) agent that is differentially retained within malignant solid tumor tissue, and either (a) performing in situ tumor vaccination in the subject by introducing into at least one of the malignant solid tumors one or more agents capable of stimulating specific immune cells within the tumor microenvironment, or (b) performing immunotherapy in the subject by systemically administering to the subject an immunostimulatory agent, such as an immune checkpoint inhibitor. In a non-limiting example, the radioactive phospholipid ether metal chelate or radiohalogenated phospholipid ether has the formula: ##STR00001##
wherein R.sub.1 comprises a chelating agent that is chelated to a metal atom, wherein the metal atom is an alpha, beta or Auger emitting metal isotope with a half-life of greater than 6 hours and less than 30 days, or wherein R.sub.1 comprises a radioactive halogen isotope. In one such embodiment, a is 1, n is 18, m is 0, b is 1, and R.sub.2 is —N.sup.+(CH.sub.3).sub.3.

The disclosure relates to the expression of stage-specific embryonic antigen 4 (SSEA-4) on stem memory T-cells (TSCM), which can then be used as a target to isolate, activate and expand this T cell subset both in vivo and in vitro. It also relates to the pharmaceutical antibody composition binding SSEA-4 targeting TSCM, as well as methods for use thereof. The antibody of the disclosure recognises the SSEA-4 glycolipid and induces proliferation of TSCM which could be used to sort this unique population from blood for clinical expansion for adoptive T-cell transfer of T-cell receptor (TCR) transduced, chimeric antigen receptor (CAR)-T transduced or cells for haematopoietic stem cell transplant. Methods of use include, without limitation, in cancer therapies and diagnostics. Examples related to the antibody with the designation F2811.72.

The present invention relates to compositions and methods employing conjugates that include a self-assembly and disassembly (SADA) polypeptide and a binding domain. The present invention encompasses the recognition that conjugates with a SADA polypeptide have certain improved biological properties. SADA-conjugates are described, along with uses thereof (e.g., as therapeutic or diagnostic agents) and methods of manufacture.

The present disclosure, relates, in general to methods for treating solid tumors comprising administering a drug-linker-antibody conjugate, wherein the drug is a tubulin disrupting agent.

Recombinant NK cells, and especially recombinant NK-92 cells express a chimeric antigen receptor (CAR) having an intracellular domain of FcεRIγ. Notably, CAR constructs with an intracellular domain of FcεRIγ had a substantially prolonged duration of expression and significantly extended cytotoxicity over time. The CAR may be expressed from RNA and DNA, preferably as a tricistronic construct that further encodes CD16 and a cytokine to confer autocrine growth support. Advantageously, such constructs also enable high levels of transfection and expression of the recombinant proteins and provide a convenient selection marker to facilitate rapid production of recombinant NK/NK-92 cells.