Methods of screening a subject to determine whether or not they are at risk of having an adverse reaction to metal debris (ARMD), also known as adverse local tissue reaction (ALTR), methods of screening compounds for use in preventing or ameliorating such an adverse response and compounds for use in treating a subject.

The present disclosure provides compositions, methods, systems, and devices for polynucleotide processing and analyte characterization from a single cell. Such polynucleotide processing may be useful for a variety of applications. The compositions, methods, systems, and devices disclosed herein generally describe barcoded oligonucleotides, which can be bound to a bead, such as a gel bead, useful for characterizing one or more analytes including, for example, protein (e.g., cell surface or intracellular proteins) and chromatin (e.g., accessible chromatin).

A method for identifying T-cells that are antigen-specific for at least one neoantigen that is likely to be presented by class II MHC alleles on surfaces of tumor cells of a subject. Peptide sequences of tumor neoantigens are obtained by sequencing the tumor cells of the subject. The peptide sequences are input into a machine-learned presentation model to generate presentation likelihoods for the tumor neoantigens, each presentation likelihood representing the likelihood that a neoantigen is presented by the class II MHC alleles on the surfaces of the tumor cells of the subject. A subset of the neoantigens is selected based on the presentation likelihoods. T-cells that are antigen-specific for at least one of the neoantigens in the subset are identified. These T-cells can be expanded for use in T-cell therapy. TCRs of these identified T-cells can also be sequenced and cloned into new T-cells for use in T-cell therapy.

A method of treating a patient who has hepatocellular carcinoma (HCC), colorectal carcinoma (CRC), glioblastoma (GB), gastric cancer (GC), esophageal cancer, NSCLC, pancreatic cancer (PC), renal cell carcinoma (RCC), benign prostate hyperplasia (BPH), prostate cancer (PCA), ovarian cancer (OC), melanoma, breast cancer (BRCA), CLL, Merkel cell carcinoma (MCC), SCLC, Non-Hodgkin lymphoma (NHL), AML, gallbladder cancer and cholangiocarcinoma (GBC, CCC), urinary bladder cancer (UBC), and uterine cancer (UEC) includes administering to said patient a composition containing a population of activated T cells that selectively recognize cells in the patient that aberrantly express a peptide. A pharmaceutical composition contains activated T cells that selectively recognize cells in a patient that aberrantly express a peptide, and a pharmaceutically acceptable carrier, in which the T cells bind to the peptide in a complex with an MHC class I molecule, and the composition is for treating the patient who has HCC, CRC, GB, GC, esophageal cancer, NSCLC, PC, RCC, BPH, PCA, OC, melanoma, BRCA, CLL, MCC, SCLC, NHL, AML, GBC, CCC, UBC, and/or UEC. A method of treating a patient who has HCC, CRC, GB, GC, esophageal cancer, NSCLC, PC, RCC, BPH, PCA, OC, melanoma, BRCA, CLL, MCC, SCLC, NHL, AML, GBC, CCC, UBC, and/or UEC includes administering to said patient a composition comprising a peptide in the form of a pharmaceutically acceptable salt, thereby inducing a T-cell response to the HCC, CRC, GB, GC, esophageal cancer, NSCLC, PC, RCC, BPH, PCA, OC, melanoma, BRCA, CLL, MCC, SCLC, NHL, AML, GBC, CCC, UBC, and/or UEC.

The invention concerns a device for tumour antigen identification and a method for tumour antigen identification; a tumour antigen identified following use of said device and/or method; a pharmaceutical composition comprising said tumour antigen; a method of treating cancer using said device and/or said method; a method of stratifying patients for cancer treatment using said device and/or said method; a treatment regimen involving stratifying patients for cancer treatment using said device and/or method and then administering a cancer therapeutic; and a tumour antigen identified using said device and/or said method for use as a cancer vaccine or immunogenic agent or cancer therapy.

MHC multimer expression constructs are provided that contiguously encode an MHC-binding peptide, MHC molecule chains and a multimerization domain in the construct such that expression in a host cell results in production of peptide-loaded MHC (pMHC) multimers by the host cell. The multimers can further comprise oligonucleotide barcodes. Peptide exchange can be performed with a plurality of pMHC multimers to create pMHC multimer libraries. Methods of making and using the pMHC multimers and libraries are also provided. Peptide-loaded MHC Class I and MHC Class II multimers, and libraries thereof, are provided.

A system for selecting an immunogenic peptide composition comprising a processor and a memory storing processor-executable instructions that, when executed by the processor, cause the processor to create a first peptide set by selecting a plurality of base peptides, wherein at least one peptide of the plurality of base peptides is associated with a disease, create a second peptide set by adding to the first peptide set a modified peptide, wherein the modified peptide comprises a substitution of at least one residue of a base peptide selected from the plurality of base peptides, and create a third peptide set by selecting a subset of the second peptide set, wherein the selected subset of the second peptide set has a predicted vaccine performance, wherein the predicted vaccine performance has a population coverage above a predetermined threshold, and wherein the subset comprises at least one peptide of the second peptide set.

The present disclosure relates to a method of isolating extracellular vesicles directly from human tissues. The invention further relates to a method of identifying disease and tissue specific membrane proteins on extracellular vesicles by membrane isolation and proteomic analysis. The invention further relates to methods of diagnosing diseases by capturing extracellular vesicles by the use of disease specific membrane proteins from body fluids, and detecting or analyzing molecular signatures (proteome, DNA, and RNA) on captured extracellular vesicles. Moreover, the present invention relates to kits, apparatus and software required for implementing aforementioned methods.

A method of treating a patient who has hepatocellular carcinoma (HCC), colorectal carcinoma (CRC), glioblastoma (GB), gastric cancer (GC), esophageal cancer, NSCLC, pancreatic cancer (PC), renal cell carcinoma (RCC), benign prostate hyperplasia (BPH), prostate cancer (PCA), ovarian cancer (OC), melanoma, breast cancer (BRCA), CLL, Merkel cell carcinoma (MCC), SCLC, Non-Hodgkin lymphoma (NHL), AML, gallbladder cancer and cholangiocarcinoma (GBC, CCC), urinary bladder cancer (UBC), and uterine cancer (UEC) includes administering to said patient a composition containing a population of activated T cells that selectively recognize cells in the patient that aberrantly express a peptide. A pharmaceutical composition contains activated T cells that selectively recognize cells in a patient that aberrantly express a peptide, and a pharmaceutically acceptable carrier, in which the T cells bind to the peptide in a complex with an MHC class I molecule, and the composition is for treating the patient who has HCC, CRC, GB, GC, esophageal cancer, NSCLC, PC, RCC, BPH, PCA, OC, melanoma, BRCA, CLL, MCC, SCLC, NHL, AML, GBC, CCC, UBC, and/or UEC. A method of treating a patient who has HCC, CRC, GB, GC, esophageal cancer, NSCLC, PC, RCC, BPH, PCA, OC, melanoma, BRCA, CLL, MCC, SCLC, NHL, AML, GBC, CCC, UBC, and/or UEC includes administering to said patient a composition comprising a peptide in the form of a pharmaceutically acceptable salt, thereby inducing a T-cell response to the HCC, CRC, GB, GC, esophageal cancer, NSCLC, PC, RCC, BPH, PCA, OC, melanoma, BRCA, CLL, MCC, SCLC, NHL, AML, GBC, CCC, UBC, and/or UEC.

Provided herein are compositions and methods for detecting the binding of a peptide to an MHC molecule, and the binding of a peptide:MHC complex to a TCR. In preferred embodiments, the compositions and methods are in a highly-multiplexed way. The compositions and methods disclosed herein can be used to provide direct information on which peptides are bound to an MHC molecule. Also provided is a method for simultaneously detecting a large number of peptides for binding to an MHC molecule and/or a T cell. A method for detecting competitive binding of a large number of peptides to an MHC molecule and/or a T cell is also disclosed. Also provided herein is a method for simultaneously detecting a large number of specific TCRs. The compositions and methods of the present invention are useful for vaccine design, research and monitoring of autoimmune and infectious disease, immunogenicity testing of therapeutics, and tissue typing.