Abstract: The present disclosure provides a composition comprising a solid support, a plurality of tethered oligonucleotides attached to the solid support, and a plurality of untethered oligonucleotides hybridized to the tethered oligonucleotides. An untethered oligonucleotide can comprise, attached via the 5? end, a cell, or an effector molecule. Hybridization of an untethered oligonucleotide to a tethered oligonucleotide generates an enzyme cleavage site, which allows for temporally controlled removal of an effector molecule. The present disclosure provides methods of temporally modulating the activity and/or phenotype of a cell. The present disclosure provides a solid support comprising patterned tethered oligonucleotides attached thereto; and methods of making the solid support.

Abstract: The present invention provides a chimeric antigen receptor (CAR) comprising: (i) a B cell maturation antigen (BCMA)-binding domain which comprises at least part of a proliferation-inducing ligand (APRIL); (ii) a spacer domain (iii) a transmembrane domain; and (iv) an intracellular T cell signaling domain. The invention also provides the use of such a T-cell expressing such a CAR in the treatment of plasma-cell mediated diseases, such as multiple myeloma.

Abstract: The present invention provides a bi-specific molecule which comprises: (i) a first domain which binds B cell maturation antigen (BCMA) and comprises at least part of a proliferation-inducing ligand (APRIL); and (ii) a second domain capable of activating a T cell. The invention also provides the use of such a molecule in the treatment of plasma-cell mediated diseases, such as multiple myeloma.

Abstract: Methods are provided for determining prognosis of multiple myeloma in a patient by measuring expression of BCMA in a sample. Also provided are methods for treating multiple myeloma by measuring expression of BCMA in a sample and administering an effective amount of an antigen binding protein that binds BCMA. Also provided are kits for measuring BCMA expression in a sample.

Abstract: The present invention provides a chimeric antigen recept- or (CAR) comprising: (i) a B cell maturation antigen (BCMA)-binding domain which comprises at least part of a proliferation-inducing ligand (APRIL); (ii) a spacer domain (iii) a transmembrane domain; and (iv) an intracellular T cell signaling domain. The invention also provides the use of such a T-cell expressing such a CAR in the treatment of plasma-cell mediated diseases, such as multiple myeloma.

Abstract: The present invention provides a chimeric antigen receptor (CAR) comprising; (i) a B cell maturation antigen (BCMA)-binding domain which comprises at least part of a proliferation-inducing ligand (APRIL); (ii) a spacer domain (iii) a transmembrane domain; and (iv) an intracellular T cell signaling domain. The invention also provides the use of such a T-cell expressing such a CAR in the treatment of plasma-cell mediated diseases, such as multiple myeloma.

Abstract: The present invention provides a variant proliferation-inducing ligand (APRIL) which has a higher binding affinity to BCMA than wild-type APRIL; and/or altered binding kinetics compared with wild-type APRIL, and/or a higher BCMA:TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) binding ratio than wild-type APRIL and which comprises mutations at one or more of the following positions: A125, V174, T175, M200, P201, S202, H203, D205 and R206.

Abstract: The present invention provides a variant proliferation-inducing ligand (APRIL), which has a higher binding affinity to BCMA than wild-type APRIL; and/or altered binding kinetics compared with wild-type APRIL, and/or a higher BCMA:TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) binding ratio than wild-type APRIL and which comprises mutations at one or more of the following positions: A125, V174, T175, M200, P201, S202, H203, D205 and R206.

Abstract: Devices for separating constituents (e.g., cells) in a fluid sample are provided. The device includes a microfluidic conduit configured to carry a flow of a fluid sample and includes two or more separation elements, each separation element including a first region and a second region, where the first region has a cross-sectional area less than a cross-sectional area of the second region. The device also includes a flow resistive element in fluid communication with the microfluidic conduit in a region between two adjacent separation elements. Also provided are methods of using the devices, as well as systems and kits that include the devices. The devices, systems, methods and kits find use in a variety of different applications, including diagnostic assays.

Abstract: The present invention provides a chimeric antigen receptor (CAR) comprising; (i) a B cell maturation antigen (BCMA)-binding domain which comprises at least part of a proliferation-inducing ligand (APRIL); (ii) a spacer domain (iii) a transmembrane domain; and (iv) an intracellular T cell signaling domain. The invention also provides the use of such a T-cell expressing such a CAR in the treatment of plasma-cell mediated diseases, such as multiple myeloma.

Abstract: The present invention provides a chimeric antigen receptor (CAR) comprising: (i) a B cell maturation antigen (BCMA)-binding domain which comprises at least part of a proliferation-inducing ligand (APRIL); (ii) a spacer domain (iii) a transmembrane domain; and (iv) an intracellular T cell signaling domain. The invention also provides the use of such a T-cell expressing such a CAR in the treatment of plasma-cell mediated diseases, such as multiple myeloma.

Abstract: Methods are provided for determining prognosis of multiple myeloma in a patient by measuring expression of BCMA in a sample. Also provided are methods for treating multiple myeloma by measuring expression of BCMA in a sample and administering an effective amount of an antigen binding protein that binds BCMA. Also provided are kits for measuring BCMA expression in a sample.

Abstract: Devices for separating constituents (e.g., cells) in a fluid sample are provided. The device includes a microfluidic conduit configured to carry a flow of a fluid sample and includes two or more separation elements, each separation element including a first region and a second region, where the first region has a cross-sectional area less than a cross-sectional area of the second region. The device also includes a flow resistive element in fluid communication with the microfluidic conduit in a region between two adjacent separation elements. Also provided are methods of using the devices, as well as systems and kits that include the devices. The devices, systems, methods and kits find use in a variety of different applications, including diagnostic assays.

Abstract: The present invention provides a variant proliferation-inducing ligand (APRIL), which has a higher binding affinity to BCMA than wild-type APRIL; and/or altered binding kinetics compared with wild-type APRIL, and/or a higher BCMA:TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) binding ratio than wild-type APRIL and which comprises mutations at one or more of the following positions: A125, V174, T175, M200, P201, S202, H203, D205 and R206.

Abstract: Devices for detecting a particle in a fluid sample are provided. The device includes a segmented microfluidic conduit configured to carry a flow of a fluid sample, where the conduit includes one or more nodes and two or more sections, and a node is positioned between adjacent sections of the conduit. The device also includes a detector configured to detect a change in current through the conduit. Also provided are methods of using the devices as well as systems and kits that include the devices. The devices, systems and methods find use in a variety of different applications, including diagnostic assays.

Abstract: The present invention provides a variant proliferation-inducing ligand (APRIL), which has a higher binding affinity to BCMA than wild-type APRIL; and/or altered binding kinetics compared with wild-type APRIL, and/or a higher BCMA:TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) binding ratio than wild-type APRIL and which comprises mutations at one or more of the following positions: A125, V174, T175, M200, P201, S202, H203, D205 and R206.

Abstract: The present invention provides a bi-specific molecule which comprises: (i) a first domain which binds B cell maturation antigen (BCMA) and comprises at least part of a proliferation-inducing ligand (APRIL); and (ii) a second domain capable of activating a T cell. The invention also provides the use of such a molecule in the treatment of plasma-cell mediated diseases, such as multiple myeloma.

Abstract: The present invention provides a chimeric antigen receptor (CAR) comprising: (i) a B cell maturation antigen (BCMA)-binding domain which comprises at least part of a proliferation-inducing ligand (APRIL); (ii) a spacer domain (iii) a transmembrane domain; and (iv) an intracellular T cell signaling domain. The invention also provides the use of such a T-cell expressing such a CAR in the treatment of plasma-cell mediated diseases, such as multiple myeloma.

Abstract: Devices for detecting a particle in a fluid sample are provided. The device includes a segmented microfluidic conduit configured to carry a flow of a fluid sample, where the conduit includes one or more nodes and two or more sections, and a node is positioned between adjacent sections of the conduit. The device also includes a detector configured to detect a change in current through the conduit. Also provided are methods of using the devices as well as systems and kits that include the devices. The devices, systems and methods find use in a variety of different applications, including diagnostic assays.

Abstract: Devices for detecting a particle in a fluid sample are provided. The device includes a segmented microfluidic conduit configured to carry a flow of a fluid sample, where the conduit includes one or more nodes and two or more sections, and a node is positioned between adjacent sections of the conduit. The device also includes a detector configured to detect a change in current through the conduit. Also provided are methods of using the devices as well as systems and kits that include the devices. The devices, systems and methods find use in a variety of different applications, including diagnostic assays.