Antibody molecules that specifically bind to PD-1 are disclosed. The anti-PD-1 antibody molecules can be used to treat, prevent and/or diagnose cancerous or infectious conditions and disorders.

The invention provides a method for treating cancer in which a level of reduced folate carrier (RFC) or folylpolyglutamate synthetase (FPGS) in cancer cells of the biopsy is determined. If the level of RFC or FPGS in the cancer cells is below a threshold value, the cancer is treated with an inhibitor of serine-hydroxymethyl-transferase (SHMT)1. If the level of RFC or FPGS in the cancer cells is above the threshold value, the cancer is treated with an inhibitor of SHMT2.

The present invention relates autoantibody biomarkers, kits, and methods for increasing the accuracy of a cancer or autoimmune screening of a subject suspected of having cancer or an autoimmune condition.

The disclosure relates to biomarkers predictive of a patient's cancer responsiveness to an immune checkpoint inhibitor therapy. The disclosure provides, in some embodiments, diagnostic and/or prognostic methods of using such biomarkers for determining whether a cancer patient would benefit from being treated with an aryl hydrocarbon receptor antagonist. In some embodiments, the biomarkers described herein may be used to inform and provide effective therapeutic methods for treating cancer comprising administering an aryl hydrocarbon receptor antagonist, optionally in combination with an immune checkpoint inhibitor therapy.

A method of predicting the risk of recurrence in a subject undergoing treatment for, or having undergone treatment for, clear cell renal cell carcinoma (ccRCC), by comparing the level of extracellular vesicles, preferably microvesicles, expressing carbonic anhydrase 9 (CA9.sup.+ MVs) in a sample from the subject with a reference level. Also, a method of diagnosing ccRCC or identifying a risk of developing ccRCC, by comparing the level of CA9.sup.+ MVs in a sample from the subject with a reference level.

Systems and methods for predicting an immune response against a tumor in a patient having the tumor are provided. The relative mass or changes of mass of tumor cells or immune cell in the tumor can be ex vivo observed, and an immune status of the tumor can be determined based on the mass of tumor cells or immune cell. The immune status can provide a guidance to predict the immune response against the tumor in the patient.

Techniques for identifying and enumerating candidate target cells within a biological fluid specimen are described. A digital image of the biological fluid specimen is received, and one or more candidate regions of pixels in the digital image are identified by identifying connected regions of pixels of a minimum intensity having a size between a minimum size and a maximum size and an aspect ratio that meets a threshold. For each candidate region of at least one of the one or more candidate region, whether the portion of the image corresponding to the candidate region includes more than a threshold number of intensity levels is determined. If the portion of the image corresponding to the candidate region includes more than the threshold number of intensity levels the portion of the image is continued to be treated as a candidate for classification.

The present invention relates to a set of polypeptides and its uses. In particular, the present invention relates to a set of polypeptides whereby this set comprises two polypeptides each of which comprises a targeting moiety “T” binding to an antigen “A” and a fragment of “F” of a functional domain, wherein said two polypeptides are not associated with each other in absence of a substrate that has “A” at (on) its surface and wherein, upon dimerization of “F”, the resulting dimer becomes functional. Furthermore, medical and diagnostic uses of said set are described. Moreover, the present invention relates to nucleic acid molecule(s) encoding said set of polypeptides. The present invention also relates to a vector comprising the nucleotide sequence of nucleic acid molecule(s) encoding said set of polypeptides. Furthermore, the present invention relates to pharmaceutical compositions comprising said set of polypeptides. Moreover, the present invention relates to a kit comprising said set of polypeptides.

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

Heritable pathogenic variants in the mismatch repair (MMR) pathway, also known as Lynch Syndrome (LS), can lead to the development of colon cancer and other cancers. Following mismatch, a complex of proteins consisting of MLH1, MSH2, MSH6 and PMS2 translocate into the nucleus to signal recruitment of repair mechanisms. Flow cytometry-based, functional variant assays (FVAs), were developed to determine whether variants in these MMR repair genes and/or other related genes would augment the nuclear translocation of MLH1 and MSH2 and downstream nuclear phosphorylation of ATM and ATR in response to DNA mismatches. Each assay distinguished pathogenic variants in MMR repair genes (MLH1, MSH2, PMS2 and MSH6) from benign controls. The combination of multiple assays provided robust separation between heterozygous pathogenic variant carriers and benign controls. The ability to produce distinct molecular phenotypes by these assays suggest FVA assays of MMR pathways could be used to identify LS and associated risk of colon and other cancers and could act as an adjunct to MMR gene sequencing panels in categorizing variants.