Abstract: The present invention relates to autologous dual-specific lymphocytes, methods of making and uses for the treatment of tumors. In particular, the invention relates to methods producing autologous dual-specific lymphocytes comprising an endogenous receptor for at least one tumor associated antigen and an exogenous receptor for a strong antigen.

Abstract: A method of decreasing cytokine production and release is disclosed. In one embodiment, the method comprises the step of providing cytotoxic cells to a subject wherein the cells are preferably natural killer cells or T lymphocytes and are genetically modified to express a chimeric antigen receptor comprising a first element that is an extracellular antigen receptor and a second intracellular element that is a signaling moiety comprising altered ADAP-dependent or Fyn-dependent signaling such that downstream signaling causing cytokine release is decreased. Specific modifications of CD137 and NKG2D cytoplasmic tails are described. Additionally, methods to develop and screen drug compounds capable of compromising the binding between ADAP and Fyn and disrupting the downstream release of cytokines are described.

Abstract: Methods of creating cells expressing specific platelet alloantigens by combining gene editing techniques and cell culture differentiation or expansion techniques employing pluripotent cells, including the steps of transfecting pluripotent cells with a plasmid encoding one or more guide RNAs targeting within a platelet alloantigen target locus and a nuclease in the presence of an HDR repair oligo and culturing the resulting cells to expand their numbers or to create a differentiated cell type of interest.

Abstract: Methods and kits for measuring levels of von Willebrand factor function in a sample without using a platelet aggregation agonist, such as ristocetin, comprising recombinant glycoprotein Ib? having a combination of G233V, D235Y and M239V mutations and an agent to detect a complex between the recombinant glycoprotein Ib? and von Willebrand factor.

Abstract: The present invention provides a method of detecting platelet activation in a patient, the method comprising the steps of a) obtaining a blood sample from a patient suspected of having heparin-induced thrombocytopenia (HIT); b) incubating an effective amount of platelet factor 4 (PF4) with a sample of platelets to yield a sample of PF4-treated platelets; c) contacting the patient blood sample with the PF4-treated platelets; and d) measuring the extent of platelet activation, wherein an increase in platelet activation compared with results obtained using a normal blood sample is indicative of the patient having HIT.