Abstract: Modified natural killer (NK) or T cells expressing hematopoietic growth factor receptors are provided. In some aspects, the modified NK cells or T cells express a thrombopoietin receptor, an erythropoietin receptor, or a chimeric polypeptide including an extracellular domain of a thrombopoietin receptor, a transmembrane domain, and an intracellular domain including an interleukin-2 receptor beta intracellular signaling domain. Methods of treating a subject with cancer are also provided, including administering the modified NK cells or T cells to the subject in combination with a thrombopoietin receptor agonist or erythropoietin receptor agonist, and in some example, interleukin-2, particularly reduced or low-dose amounts of IL-2.

Abstract: Modified NK cells with reduced expression of CCR5 are provided. Methods of treating a subject with cancer with the modified NK cells are also provided. In some examples, the modified NK cells also have reduced expression of one or more of CCR1, CXCR6, and CD38, increased expression of one or more of CXCR4, CCR7, and CXCR3, and/or express a chimeric antigen receptor.

Abstract: Disclosed herein are T cell receptors (TCRs) capable of binding an antigen expressed by renal cell carcinoma cells. In some examples, the TCRs include an ? chain (such as SEQ ID NO: 2) and a ? chain (such as SEQ ID NO: 3). Also disclosed herein are vectors including nucleic acids encoding the disclosed TCR ? and/or ? chains. Further disclosed are modified T cells expressing the TCRs. In some examples, the modified T cells are prepared by transducing T cells with a vector including nucleic acids encoding the TCR ? chain and the TCR ? chain. In some embodiments, methods include treating a subject with RCC, by obtaining a population of T cells, transducing the population of T cells with a vector including a nucleic acids encoding the TCR ? chain and the TCR ? chain, and administering a composition comprising the modified T cells to the subject.

Abstract: Modified natural killer (NK) or T cells expressing hematopoietic growth factor receptors are provided. In some embodiments, the NK cells or T cells express a thrombopoietin receptor or an erythropoietin receptor. Methods of treating a subject with cancer are also provided, including administering the modified NK cells or T cells to the subject in combination with a thrombopoietin receptor agonist or erythropoietin receptor agonist, and in some example, interleukin-2, particularly reduced or low-dose amounts of IL-2.

Abstract: Disclosed herein are method of producing NK cells that include one or more heterologous nucleic acids. The methods include culturing a population of isolated NK cells in the presence of one or more cytokines to produce a population of activated NK cells. The population of activated NK cells are transduced with a viral vector comprising the one or more heterologous nucleic acids, for example by contacting the activated NK cells with viral particles including the viral vector. The resulting transduced NK cells are then cultured in the presence of one or more cytokines, and optionally in the presence of irradiated feeder cells, to produce a population of expanded transduced NK cells. Also disclosed are methods of treating a subject with a disorder (such as a tumor or hyperproliferative disorder) by administering to the subject NK cells produced by the methods described herein.

Abstract: Disclosed herein are method of producing NK cells that include one or more heterologous nucleic acids. The methods include culturing a population of isolated NK cells in the presence of one or more cytokines to produce a population of activated NK cells. The population of activated NK cells are transduced with a viral vector comprising the one or more heterologous nucleic acids, for example by contacting the activated NK cells with viral particles including the viral vector. The resulting transduced NK cells are then cultured in the presence of one or more cytokines, and optionally in the presence of irradiated feeder cells, to produce a population of expanded transduced NK cells. Also disclosed are methods of treating a subject with a disorder (such as a tumor or hyperproliferative disorder) by administering to the subject NK cells produced by the methods described herein.

Abstract: Disclosed herein are method of producing NK cells that include one or more heterologous nucleic acids. The methods include culturing a population of isolated NK cells in the presence of one or more cytokines to produce a population of activated NK cells. The population of activated NK cells are transduced with a viral vector comprising the one or more heterologous nucleic acids, for example by contacting the activated NK cells with viral particles including the viral vector. The resulting transduced NK cells are then cultured in the presence of one or more cytokines, and optionally in the presence of irradiated feeder cells, to produce a population of expanded transduced NK cells. Also disclosed are methods of treating a subject with a disorder (such as a tumor or hyperproliferative disorder) by administering to the subject NK cells produced by the methods described herein.

Abstract: Disclosed herein are modified NK cells, compositions comprising modified NK cells, and methods for treating a tumor or hyperproliferative disease in a subject. In some embodiments, the modified NK cells include NK cells including a heterologous nucleic acid molecule encoding a CD16 protein comprising a valine at amino acid position 158 (CD16-V158), a heterologous nucleic acid molecule encoding a CCR7 protein, or both. In some embodiments, methods include treating a subject with a tumor by administering a composition comprising an anti-cancer monoclonal antibody and administering a composition comprising the modified NK cells to the subject. Also disclosed are methods of making modified NK cells by obtaining a population of NK cells from a subject and transfecting the population of NK cells with a heterologous nucleic acid molecule encoding CD16-V158, a heterologous nucleic acid molecule encoding a CCR7 protein, or both.

Abstract: Disclosed herein are modified NK cells, compositions comprising modified NK cells, and methods for treating a tumor or hyperproliferative disease in a subject. In some embodiments, the modified NK cells include NK cells including a heterologous nucleic acid molecule encoding a CD16 protein comprising a valine at amino acid position 158 (CD16-V158), a heterologous nucleic acid molecule encoding a CCR7 protein, or both. In some embodiments, methods include treating a subject with a tumor by administering a composition comprising an anti-cancer monoclonal antibody and administering a composition comprising the modified NK cells to the subject. Also disclosed are methods of making modified NK cells by obtaining a population of NK cells from a subject and transfecting the population of NK cells with a heterologous nucleic acid molecule encoding CD16-V158, a heterologous nucleic acid molecule encoding a CCR7 protein, or both.

Abstract: Disclosed herein are T cell receptors (TCRs) capable of binding an antigen expressed by renal cell carcinoma cells. In some examples, the TCRs include an ? chain (such as SEQ ID NO: 2) and a ? chain (such as SEQ ID NO: 3). Also disclosed herein are vectors including nucleic acids encoding the disclosed TCR ? and/or ? chains. Further disclosed are modified T cells expressing the TCRs. In some examples, the modified T cells are prepared by transducing T cells with a vector including nucleic acids encoding the TCR ? chain and the TCR ? chain. In some embodiments, methods include treating a subject with RCC, by obtaining a population of T cells, transducing the population of T cells with a vector including a nucleic acids encoding the TCR ? chain and the TCR ? chain, and administering a composition comprising the modified T cells to the subject.

Abstract: Disclosed herein are modified NK cells, compositions comprising modified NK cells, and methods for treating a tumor or hyperproliferative disease in a subject. In some embodiments, the modified NK cells include NK cells including a heterologous nucleic acid molecule encoding a CD16 protein comprising a valine at amino acid position 158 (CD16-V158), a heterologous nucleic acid molecule encoding a CCR7 protein, or both. In some embodiments, methods include treating a subject with a tumor by administering a composition comprising an anti-cancer monoclonal antibody and administering a composition comprising the modified NK cells to the subject. Also disclosed are methods of making modified NK cells by obtaining a population of NK cells from a subject and transfecting the population of NK cells with a heterologous nucleic acid molecule encoding CD16-V158, a heterologous nucleic acid molecule encoding a CCR7 protein, or both.

Abstract: Provided herein are methods of inhibiting growth or proliferation of cells expressing CD38 by contacting the CD38-expressing cells with 1) NK cells bound to an anti-CD38 F(ab?)2 fragment and 2) an anti-CD38 antibody, in either order or simultaneously. Also provided herein are methods of treating or inhibiting a hyperproliferative disorder or an autoimmune disorder in a subject by administering to the subject 1) NK cells bound to an anti-CD38 F(ab?)2 fragment and 2) an anti-CD38 antibody, in either order or simultaneously.

Abstract: Provided herein are methods of inhibiting growth or proliferation of cells expressing CD38 by contacting the CD38-expressing cells with 1) NK cells bound to an anti-CD38 F(ab?)2 fragment and 2) an anti-CD38 antibody, in either order or simultaneously. Also provided herein are methods of treating or inhibiting a hyperproliferative disorder or an autoimmune disorder in a subject by administering to the subject 1) NK cells bound to an anti-CD38 F(ab?)2 fragment and 2) an anti-CD38 antibody, in either order or simultaneously.

Abstract: Disclosed herein are method of producing NK cells that include one or more heterologous nucleic acids. The methods include culturing a population of isolated NK cells in the presence of one or more cytokines to produce a population of activated NK cells. The population of activated NK cells are transduced with a viral vector comprising the one or more heterologous nucleic acids, for example by contacting the activated NK cells with viral particles including the viral vector. The resulting transduced NK cells are then cultured in the presence of one or more cytokines, and optionally in the presence of irradiated feeder cells, to produce a population of expanded transduced NK cells. Also disclosed are methods of treating a subject with a disorder (such as a tumor or hyperproliferative disorder) by administering to the subject NK cells produced by the methods described herein.

Abstract: Methods and apparatus for selectively accessing a portion of a sterile cryopreserved sample are disclosed. The apparatus may include a container configured to receive the cryopreserved sample and having a first portion and a second portion, a heat sink chamber surrounding the first portion of the container, and a heat source adjacent to the second portion of the container. The chamber may be configured to maintain a non-accessed portion of the sample in a cryopreserved state. The heat source may be configured to separating an accessed portion of the sample from the non-accessed portion of the sample while maintaining the viability of the accessed portion while the non-accessed portion is maintained in the cryopreserved state.

Abstract: Methods and apparatus for selectively accessing a portion of a sterile cryopreserved sample are disclosed. The apparatus may include a container configured to receive the cryopreserved sample and having a first portion and a second portion, a heat sink chamber surrounding the first portion of the container, and a heat source adjacent to the second portion of the container. The chamber may be configured to maintain a non-accessed portion of the sample in a cryopreserved state. The heat source may be configured to separating an accessed portion of the sample from the non-accessed portion of the sample while maintaining the viability of the accessed portion while the non-accessed portion is maintained in the cryopreserved state.

Abstract: Methods and apparatus for selectively accessing a portion of a sterile cryopreserved sample are disclosed. The apparatus may include a container configured to receive the cryopreserved sample and having a first portion and a second portion, a heat sink chamber surrounding the first portion of the container, and a heat source adjacent to the second portion of the container. The chamber may be configured to maintain a non-accessed portion of the sample in a cryopreserved state. The heat source may be configured to separating an accessed portion of the sample from the non-accessed portion of the sample while maintaining the viability of the accessed portion while the non-accessed portion is maintained in the cryopreserved state.

Abstract: Methods and apparatus for selectively accessing a portion of a sterile cryopreserved sample are disclosed. The apparatus may include a container configured to receive the cryopreserved sample and having a first portion and a second portion, a heat sink chamber surrounding the first portion of the container, and a heat source adjacent to the second portion of the container. The chamber may be configured to maintain a non-accessed portion of the sample in a cryopreserved state. The heat source may be configured to separating an accessed portion of the sample from the non-accessed portion of the sample while maintaining the viability of the accessed portion while the non-accessed portion is maintained in the cryopreserved state.