Abstract: The present disclosure provides methods and compositions for determining the antigen specificity of T cells and in a scalable, high-throughput approach. The disclosure provides methods for producing RNA-barcoded pMHC multimers that can be decoded using single-cell RNA sequencing methods. Among these, disclosed herein are multivalent virus-like-particles bound with pMHC in E. coli cells that encapsulate an RNA barcode encoding the peptide identity.

Abstract: The subject matter disclosed herein is generally directed to CD8+ tumor infiltrating lymphocytes comprising gene signatures associated with response to immunotherapy treatment. Moreover, the subject matter disclosed herein is generally directed to methods and compositions for use of the gene signatures. Specifically, disclosed herein are gene signatures associated with response to checkpoint blockade therapy and immune cell subtypes characterized by said gene signatures. Further disclosed are methods of using said gene signatures and immune cell subtypes. Further disclosed are pharmaceutical compositions comprising populations of CD8+ TILs enriched for a specific subtype.

Abstract: The present invention discloses high-throughput methods for the creation of antibodies or antigen-binding fragments that can bind to single or multiple targets. Also disclosed are methods for using one or more antibodies or antigen-binding fragments to detect cognate binding partners in various types of samples.

Abstract: Methods and compositions for a single- or multi-pot protocol for the efficient end to end capture of RNAs (inclusive of their poly-A tail or their 3? end) is described. Capture oligonucleotides containing a 3? non-extendable end and a selectively cleavable base upstream of an oligo-dT or oligo-dN and a 5? sequence containing unique molecular identifiers, and 2) a deoxyuracil glycosylase that acts only on a deoxyuracil present in a DNA: DNA duplex or DNA/RNA heteroduplex are used. A dual template switching mechanism may be used.

Abstract: A system and method for isolating target substrates includes a microfluidic chip, comprising a plurality of processing units, each processing unit comprising: an inlet port, a plurality of first chambers connected to the inlet port by a fluid channel, the fluid channel comprising a plurality of valves, a plurality of second chambers, each of the second chambers connected to a respective first chamber by a fluid channel, each fluid channel including a controllable blocking valve, and a plurality of respective outlet ports, each outlet port in fluid communication with a respective one of said second chambers and each outlet port including a blocking valve. A magnet is adjacent the microfluidic chip and is movable relative to the microfluidic chip. A valve control is capable of actuating certain ones of the controllable blocking valves in response to a control signal.

Abstract: Disclosed herein are methods of eliciting an anti-cancer immune response by administering tumor-associated antigens, cells containing tumor-associated antigens, and/or nucleic acids encoding tumor-associated antigens. inducing immunogenic cell death in the cells expressing or containing the tumor-associated antigens. and optionally generating hyperactivated dendritic cells. Expression of tumor-associated antigens in a separate anatomical site generates a tumor avatar, which mimics the antigenic, but not immunosuppressive, environment of the tumor, with the generation of hyperactivated dendritic cells enhancing antigen presentation to elicit a robust anti-tumor T cell and antibody response. Also provided are compositions and kits containing nucleic acids and other components for use in the methods provided herein.

Abstract: Provided herein are compositions and methods for enhancing the activity of Stimulator of Interferon Genes (STING) with one or more agents for inhibiting the activity of one or more negative regulators of STING, including DNAJC13 and ESCRT.

Abstract: This disclosure provides a method and compositions for substantially increasing the concentration of DNA in macrophages of a patient. By administering to a patient one or more agents which prevent the activity of deoxyribonucleases within lysosomes of macrophages, degradation of DNA phagocytosed by macrophages is temporarily blocked, permitting its accumulation. This strategy has the potential to enhance the detection of genetic biomarkers from cells typically phagocytosed by macrophages, such as tumor cells, and thus has applications for early or residual detection of cancer.

Abstract: The disclosure provides methods of reprogramming polyclonal T cells to maintain long-term persistence. The disclosure further provides methods of treatment, such as adoptive T cell transfer therapies, that harness Tscms for development of tumor-reactive T cells. In some embodiments, the disclosure provides methods and compositions for positive modulation of the Tscm-producing phenotype, e.g., positive modulation of TCF7 expression. Positive modulation of TCF7 expression allows for maintenance of an increased T number of stem-like T cells capable of both self-renewal and generation of differentiated, cytolytic progeny.

Abstract: Systems, compositions, and methods for isolating HLA-peptides from cells. A universal platform and methods for profiling the HLA-peptidome, enabling identification of endogenously presented HLA-peptides from cell lines expressing any possible class I or II construct.

Abstract: The present disclosure relates to methods and compositions for enhanced assessment of exogenous polynucleotide and/or polypeptide-mediated transcriptional perturbations at high throughput and single cell/droplet levels of resolution. In embodiments, nucleic acid fusions of exogenous polynucleotide(s) and associated target transcript(s) are produced within individually sequestered or discretely identifiable cells/lysates and analyzed for exogenous polynucleotide mediated perturbations across a vast population of droplets/cells within individual reactions. Kits for performance of the methods are also provided.

Abstract: In one aspect, provided herein is a method comprising: (a) (i) determining cytolytic activity in a tumor from the subject; and/or (ii) determining genetic alterations associated with cytolytic activity in the tumor; and (b) administering an immunotherapeutic agent to the subject if (i) cytolytic activity is detected in the tumor and/or (ii) a genetic alteration associated with induction of cytolytic activity, tumor resistance to cytolytic activity and/or suppression of cytolytic activity is detected in the tumor.

Abstract: The present disclosure provides methods for determining signatures of immune responses to immunomodulating agents in cells and in tissues. Also provided herein are computational methods for deconvoluting gene expression profiling data. Further provided herein are methods for treating a disease or disorder (e.g, proliferative diseases such as cancer, autoimmune diseases such as rheumatoid arthritis and psoriasis, allergies, etc.) in a subject comprising administering one or more immunomodulating agents to drive an immune response, in combination with a treatment for the disease or disorder (e.g, an anti-cancer therapy, an anti-viral therapy, a vaccination, etc.).

Abstract: The present disclosure provides, in part, methods of discovering immunotherapy targets in vivo, therapeutic compositions (e.g., shRNA, immunoresponsive cells expressing shRNA and/or a chimeric antigen receptors (CAR)), and methods of use thereof.

Abstract: Compositions and methods for isolating HLA-peptides from cells. A universal platform and methods for profiling the HLA-peptidome, enabling identification of endogenously presented HLA-peptides from cell lines expressing any possible class I or II construct.

Abstract: Provided herein, in some embodiments, are methods for treating age-associated conditions, including systemic inflammation and disease, via enhanced DNA degradation.

Abstract: The present disclosure relates to compositions and methods for nucleic acid sequencing, and specifically, at least in certain aspects, provides methods and compositions for enhancing the efficacy, throughput and/or yield of known long-range sequencing platforms, by providing chimeric arrays of input sequences. Such arrays of component nucleic acid sequence elements can be prepared via methods that minimize introduction of bias. The application of the current methods to obtain isoform sequencing information, e.g., from patient samples is specifically also provided, as are methods for mitochondrial lineage tracing that employ the instant chimeric amplicon sequencing processes. Methods and systems for array nucleic acid sequence processing and interpretation are also provided.

Abstract: The present invention relates to neoplasia vaccine or immunogenic composition administered in combination with other agents, such as checkpoint blockade inhibitors for the treatment or prevention of neoplasia in a subject.

Abstract: The present disclosure relates to compositions and methods for single-cell nucleic acid sequencing, and specifically provides for pre-amplifying target nucleic acids in a manner that allows for more proportionate detection of all target nucleic acids, including low prevalence/abundance RNAs, from individual cells. The disclosure also provides for application of a series of barcoding steps to associate cell-specific identifiers (IDs) to the targeted nucleotide sequences, and ultimately provides for increased throughput capacity and greater accuracy of single-cell nucleic acid sequencing. Certain aspects of the present disclosure also provide for improved quantitative detection of nucleic acid sequence barcodes, which in embodiments allows for highly sensitive quantitative detection of barcoded antibody levels and/or highly sensitive quantitative detection of barcoded antibody-bound protein levels (e.g.

Abstract: Compositions and methods for isolating HLA-peptides from cells. A universal platform and methods for profiling the HLA-peptidome, enabling identification of endogenously presented HLA-peptides from cell lines expressing any possible class I or II construct.