Abstract: Viral vectors are provided for use as genetic immunotherapeutic agents, including preventive and therapeutic vaccines as well as compositions to enhance cellular immune responses and innate immune responses. The vectors are particularly useful for treating or preventing cancer and infectious diseases. The vectors include lentiviral vectors that encode one or more antigens, a combination of adjuvants, and optionally may encode one or more soluble and secreted checkpoint inhibitor molecules. The adjuvants include latent membrane protein 1 (LMP1) from Epstein Barr virus and a fusion protein including LMP1 with in which the intracytoplasmic domain has been replaced by human IPS1 or a variant thereof capable of activating the STING pathway. The vector-encoded sequences are codon optimized for human expression.

Abstract: Promoter sequences for use in expressing a transgene in CD3+ cells are provided. The promoter sequences can be inserted into a vector in a 5? untranslated region proximal to a transgene. The promoters are selective for expression in CD3+ cells and contain binding sites for transcription factors found in CD3+ cells. The promoters can be integrated into vectors, including polymer-encapsulated lentiviral vector nanoparticles, used to transduce T-cells for genetic immunotherapy to treat cancer and infectious diseases. The T-cell selectivity of the promoters adds an improved safety factor to the use of viral vectors for immunotherapy in vitro and in vivo.

Abstract: Viral vectors are provided for use as genetic immunotherapeutic agents, including preventive and therapeutic vaccines as well as compositions to enhance cellular immune responses. The vectors are particularly useful for treating or preventing cancer and infectious diseases. The vectors include lentiviral vectors that encode one or more antigens and an adjuvant, and optionally may encode one or more soluble checkpoint inhibitor molecules. The adjuvant is a fusion protein including latent membrane protein 1 (LMP1) from Epstein Barr virus with in which the intracytoplasmic domain has been replaced by human IPS1 or a variant thereof capable of activating the STING pathway. The vector-encoded sequences are codon optimized for human expression.

Abstract: Engineered multispecific antigen binding molecules are provided which contain two or more different aptamer moieties joined by a linker. The antigen binding molecules are capable of specifically binding to one or more antigens and bridging different cell types, such as immune cells and cancer cells. The linked aptamers can be used to modulate and enhance immune function.

Abstract: Polymer-encapsulated viral vector nanoparticles and methods of using them provide enhanced delivery of genetic material for use in gene therapy and other applications. The nanoparticles include an outer shell containing an oligopeptide-modified poly(beta-amino ester) polymer which encapsulates the vector and allows the vector to transduce cells without the need for pseudotyping or the inclusion of any viral fusion protein, such as VSV-G. The polymer-encapsulated vector nanoparticles have a natural tropism for peripheral blood cells, such as leucocytes, without the need for a targeting moiety, and have an improved safety profile compared to pseudotyped viral vectors.

Abstract: Methods for synthesizing and purifying oligopeptide-modified poly-beta-amino-esters (OM-PBAEs) and related polymers without using DMSO as a solvent yield OM-PBAEs with improved storage stability in biocompatible buffers. The polymers can be stored for extended periods and used to encapsulate nucleic acids and viral vectors losing transfection or transduction efficiency.

Abstract: High affinity aptamer sequences recognizing CD3 protein complex on cell surfaces are provided. The aptamers can be used as targeting moieties for delivery vehicles or as molecular components for immunotherapy, immunodiagnostics, or for isolating, purifying, or characterizing CD3+ T cells in a subject.

Abstract: An aptamer-based switch technology is provided that enhances control of the use of chimeric antigen receptor (CAR)-related immunotherapies. The aptamer-based switch utilizes a synthetic bridge molecule containing a target-binding aptamer bound through a linker to a CAR-binding aptamer. A system containing a CAR and a corresponding aptameric bridge provides an immunotherapy platform that: (i) can be targeted to any desired antigen by choosing the target-binding aptamer of the bridge, (ii) can be redirected from one target to another by changing the target-binding aptamer; (iii) can be dosed according to the changing needs of an individual patient overtime by altering the administration protocol for the bridge; (iv) can be switched on or off quickly or gradually; (v) can be used as a companion diagnostic for a specific CAR therapy; (vi) can be integrated with either in vivo or ex vivo CAR expression; (vii) is non-immunogenic; and (viii) has low production costs.

Abstract: The invention relates to the regulated expression of a chimeric antigen receptor (CAR) within a lentiviral vector. The CAR comprises a hook-binding domain that interacts with a hook, preferably encoded by the same lentiviral vector, which prevents proper processing and release of the CAR to the cell membrane. The invention encompasses vectors, methods of making the vectors, and methods of using them, including medicinal uses. The vectors can be used for administration to humans to induce immune responses and to treat cancers and tumors.

Abstract: The present technology relates to gene delivery vehicles comprising a retroviral vector coated with a polymer or a mixture of polymers to form a nanoparticle. The retroviral vectors comprise a transgene and in certain embodiments lack envelope protein. The technology includes a method of making the gene delivery vehicles and a method of treating a disease by administering the gene delivery vehicles.

Abstract: The invention relates to the regulated expression of a chimeric antigen receptor (CAR) within a lentiviral vector. The CAR comprises a hook-binding domain that interacts with a hook, preferably encoded by the same lentiviral vector, which prevents proper processing and release of the CAR to the cell membrane. The invention encompasses vectors, methods of making the vectors, and methods of using them, including medicinal uses. The vectors can be used for administration to humans to induce immune responses and to treat cancers and tumors.

Abstract: Viral vectors are provided for use as genetic immunotherapeutic agents, including preventive and therapeutic vaccines as well as compositions to enhance cellular immune responses and innate immune responses. The vectors are particularly useful for treating or preventing cancer and infectious diseases. The vectors include lentiviral vectors that encode one or more antigens, a combination of adjuvants, and optionally may encode one or more soluble and secreted checkpoint inhibitor molecules. The adjuvants include latent membrane protein 1 (LMP1) from Epstein Barr virus and a fusion protein including LMP1 with in which the intracytoplasmic domain has been replaced by human IPS1 or a variant thereof capable of activating the STING pathway. The vector-encoded sequences are codon optimized for human expression.

Abstract: Methods of making lyophilized lentiviral vector particles are provided. Compositions comprising lyophilized lentiviral vector particles are also provided. Methods of administering a lentiviral vector particle to a subject and uses of lentiviral vector particle compositions are also provided.

Abstract: Viral vectors are provided for use as genetic immunotherapeutic agents, including preventive and therapeutic vaccines as well as compositions to enhance cellular immune responses. The vectors are particularly useful for treating or preventing cancer and infectious diseases. The vectors include lentiviral vectors that encode one or more antigens and an adjuvant, and optionally may encode one or more soluble checkpoint inhibitor molecules. The adjuvant is a fusion protein including latent membrane protein 1 (LMP1) from Epstein Barr virus with in which the intracytoplasmic domain has been replaced by human IPS1 or a variant thereof capable of activating the STING pathway. The vector-encoded sequences are codon optimized for human expression.

Abstract: The invention relates to a novel use of a Bordetella adenylcyclase toxin in the manufacturing of vectors for targeting in vivo a molecule of interest, specifically to CD11b expressing cells. The invention also relates to an immunogenic composition that primes immune responses, to pharmaceutical compositions and to a new vector for molecule delivery to CD11b expressing cells.

Abstract: The present invention relates to compositions, methods, and uses employing lentiviral vector particles for induction of an immune response by administration to a human, wherein the lentiviral vector particles comprise a lentiviral vector, wherein the DNA of the lentiviral vector comprises a promoter directing expression of a HTLV-1 p12p30-Tax-HBZ fusion protein. The invention encompasses these vectors, methods of making the vectors, and methods of using them, including medicinal uses.

Abstract: The invention encompasses a lentiviral packaging vector comprising a non-subtype B gag-pol sequence, particularly a subtype D gag-pol sequence. The invention further encompasses methods for making and using these vectors. The invention further encompasses lentiviral vector particles comprising HIV-1 non-subtype B Gag and/or Pol proteins.

Abstract: The invention encompasses a lentiviral packaging vector comprising a non-subtype B gag-pol sequence, particularly a subtype D gag-pol sequence. The invention further encompasses methods for making and using these vectors. The invention further encompasses lentiviral vector particles comprising HIV-1 non-subtype B Gag and/or Pol proteins.

Abstract: The invention relates to the regulated expression of a chimeric antigen receptor (CAR) within a lentiviral vector. The CAR comprises a hook-binding domain that interacts with a hook, preferably encoded by the same lentiviral vector, which prevents proper processing and release of the CAR to the cell membrane. The invention encompasses vectors, methods of making the vectors, and methods of using them, including medicinal uses. The vectors can be used for administration to humans to induce immune responses and to treat cancers and tumors.

Abstract: The present invention relates to the insertion of an MHC class I, MHC Class II, or ?2 microglobulin upstream promoter sequence into a lentiviral vector to increase viral titers. The invention encompasses these vectors, methods of making the vectors, and methods of using them, including medicinal uses.