Abstract: The present disclosure describes an immunotherapy delivery hydrogel system. The immunotherapy delivery hydrogel system can be degradable and can release therapeutic agents at a tunable rate, and in a controlled manner. The immunotherapy delivery hydrogel system includes a hydrogel matrix and cancer therapeutic agent(s) associated with the hydrogel matrix. The hydrogel system can further include tumor cell-attractant(s) conjugated to the hydrogel matrix. The tumor cell-attractant(s) and the cancer therapeutic agent(s) act synergistically to treat cancer.

Abstract: Genomic safe harbors (GSH) for genetic therapies in human stem cells and engineered nanoparticles to provide targeted genetic therapies are described. The GSH and/or associated nanoparticles can be used to safely and efficiently treat a variety of genetic, infectious, and malignant diseases.

Abstract: Systems and methods to genetically modify B cells to express selected antibodies are described. The systems and methods can be used to: obviate the need for classical vaccinations; provide protection against infectious agents for which no vaccinations are currently available; provide protection against infectious agents when patients are otherwise immune-suppressed; and/or provide a benefit provided by a therapeutic antibody, such as in the treatment of autoimmune disorders.

Abstract: Systems and methods to increase the efficacy of vaccines that require or are rendered more effective with T cell mediated immunity are described. The systems and methods utilize polynucleotides that genetically modify T cells to express a T cell receptor specific for an administered vaccine antigen.

Abstract: Described herein are peptides and variants and mutants thereof capable of interacting with TEAD, disrupting the HIPPO pathway, or modulating the activity or function of TEAD interactions in a cell. Pharmaceutical compositions and uses of peptides, as well as methods of designing and manufacturing such peptides, to treat cancer, tumor, or any other disease/condition associated with a dysregulated HIPPO pathway or uncontrolled cell growth are also described herein.

Abstract: Circular handed alpha-helical repeat proteins are described. The repeat proteins have a number of uses as scaffolds for geometrically precise, arrayed presentation of cell-signaling or immune-related protein and peptide epitopes, as well as numerous other therapeutic, diagnostic, and nanotechnological uses.

Abstract: The present disclosure provides binding proteins and TCRs with high affinity and specificity against Merkel cell polyomavirus T antigen epitopes or peptides, T cells expressing such high affinity Merkel cell polyomavirus T antigen specific TCRs, nucleic acids encoding the same, and compositions for use in treating Merkel cell carcinoma.

Abstract: Systems and methods to selectively protect therapeutic cells by reducing CD33 expression in the therapeutic cells using base editors and targeting non-therapeutic cells with an anti-CD33 therapy are described. The selective protection results in the enrichment of the therapeutic cells while simultaneously targeting any diseased, malignant and/or non-therapeutic CD33 expressing cells within a subject.

Abstract: Provided herein are compositions and methods comprising mutated coronavirus “S” spike proteins or receptor binding domains thereof that have an increased expression level, yield and stability compared to its corresponding native or wild-type coronavirus spike protein under the same expression, culture or storage conditions. These mutated spike proteins can be used for generating a protein-based vaccine against one or more coronaviruses.

Abstract: The present disclosure provides compositions and methods for targeting a Ras antigen to, for example, treat or prevent cancer. Disclosed embodiments include binding proteins, such as a T cell receptor or a chimeric antigen receptor, that bind to a Ras antigen:HLA complex. Polynucleotides encoding such binding protein can introduced into a host cell, such as a T cell, and the cell can be used in immunotherapy for treating various cancers. Also provided are immunogenic polypeptides that can be useful to, for example, induce an immune response against a mutated Ras or to identify a binding protein that binds to a Ras antigen.

Abstract: Systems and methods to increase the efficacy of vaccines that require or are rendered more effective with T cell mediated immunity are described. The systems and methods utilize polynucleotides that genetically modify T cells to express a T cell receptor specific for an administered vaccine antigen.

Abstract: The present disclosure provides compositions and methods for accurately detecting mutations by uniquely tagging double stranded nucleic acid molecules with dual cyphers such that sequence data obtained from a sense strand can be linked to sequence data obtained from an anti-sense strand when sequenced, for example, by massively parallel sequencing methods.

Abstract: The present invention relates to methods, kits and compositions for expansion of embryonic hematopoietic stem cells and providing hematopoietic function to human patients in need thereof. In one aspect, it relates to kits and compositions comprising a Notch agonist, one or more growth factors, and, optionally, an inhibitor of the TGF? pathway. Also provided herein are methods for expanding embryonic hematopoietic stem cells using kits and compositions comprising a Notch agonist, one or more growth factors, and, optionally, an inhibitor of the TGF? pathway. The embryonic hematopoietic stem cells expanded using the disclosed kits, compositions and methods include cells derived from an embryo (e.g., aorta-gonad-mesonephros region of the embryo), embryonic stem cells, induced pluripotent stem cells, or reprogrammed cells of other types.

Abstract: Mutated and/or truncated malarial circumsporozoite proteins (CSP) and associated nucleic acids that are more stable and highly expressed in mammalian cells are described. The mutated and/or truncated CSP and associated nucleic acids can be expressed to produce malaria vaccine antigens.

Abstract: The disclosure provides methods for inducing Notch signaling in a targeted manner within aggregations of cells. The methods include contacting the aggregation of cells with a bi-specific molecule that facilitates trans-binding of Notch receptor. The bi-specific molecule comprising a cell-targeting domain that specifically binds to a cell-specific antigen expressed in the aggregation of cells, and a Notch-binding domain that specifically binds to Notch receptor. In some aspects, the disclosed methods and reagents provide methods of promoting pro-inflammatory states in tumor micro-environments.

Abstract: The disclosure provides methods and compositions for microlumen targeting in the treatment of cancers characterized by solid tumors or cell clusters, such as circulating tumor cell (CTC) clusters and disseminated tumor cell (DTC) clusters. The methods and compositions specifically target epigen in microlumenal space between two or more cancer cells and reduce the expression, functionality and/or concentration of epigen within the microlumenal space. The methods and compositions can be part of methods of treating cancer in a subject wherein the cancer is characterized by a solid tumor, a circulating tumor cell (CTC) cluster, and/or a disseminated tumor cell (DTC) cluster. The reduced levels of functional epigen in the microlumen result in reduced incidence of metastasis and increased susceptibility of the tumor cells to additional therapeutic interventions.

Abstract: The present disclosure provides, among other things, helper-dependent adenoviral serotype 35 (Ad35) vectors. In various embodiments, helper-dependent Ad35 vectors can be used to deliver a therapeutic payload to a subject in need thereof. Exemplary payloads can encode replacement proteins, antibodies, CARs, TCRs, small RNAs, and genome editing systems. In certain embodiments, a helper-dependent Ad35 vector is engineered for integration of a payload into a host cell genome. The present disclosure further includes methods of gene therapy that include administration of a helper-dependent Ad35 vector to a subject in need thereof.

Abstract: Methods and compositions for treatment of prostate cancers, such as androgen receptor (AR) deficient and androgen receptor (AR) low cancers, are disclosed. The methods include administration of an agent that inhibits activity of eIF4F or an agent that disrupts the eIF4F translation-initiation complex (composed of eIF4E, eIF4A, and eIF4G).

Abstract: The instant disclosure provides biomarkers and methods for identifying subjects at risk of developing cytokine release syndrome (CRS), neurotoxicity, or both after adoptive immunotherapy to guide preemptive intervention, modified therapy, or the like. For example, adverse event biomarkers may be measured in a subject before pre-conditioning chemotherapy, before immunotherapy (e.g., adoptive immunotherapy infusion comprising a chimeric antigen receptor (CAR) modified T cell), or shortly after pre-conditioning chemotherapy and/or immunotherapy. Exemplary biomarkers include temperature, cytokine levels and endothelial activation biomarkers, such as angiopoietin 2, von Willebrand factor (vWF), ratio of angiopoietin 2 to angiopoietin 1, and ratio of ADAMTS13 to vWF. Also provided are methods of treating subjects identified as at risk of developing cytokine release syndrome (CRS), neurotoxicity, or both to minimize such potential adverse events.

Abstract: A method for detecting the binding of a chromatin-associated factor of interest to a sequence of chromatin DNA in a cell, including: contacting a permeabilized cell or nucleus with a specific binding agent that specifically recognizes the chromatin-associated factor of interest, wherein the specific binding agent is linked to a nuclease that is inactive or an activatable transposome; activating the nuclease or transposase, thereby excising the sequence of chromatin DNA bound to the chromatin-associated factor of interest; isolating the excised DNA; and determining the sequence of the excised DNA, thereby detecting binding of a chromatin-associated factor of interest to a sequence of chromatin DNA in the cell.