Described herein are novel anti-PD1 antibody reagents (e.g., antibodies, antigen-binding fragments thereof, and/or chimeric antigen receptors). Also described herein antibody-drug conjugates or kits comprising the disclosed antibody reagents, as well as methods of treating cancer by administering the disclosed antibody reagents.

The invention provides PRKACB gene fusions, PRKACB fusion proteins, and fragments of those genes and polypeptides. The invention further provides methods of diagnosing and treating diseases or disorders associated wiih PRKACB fusions, such as conditions mediated by aberrant PRKACB expression or activity or overexpression of PRKACB.

The present inventors have identified specific oncogenic pathways preferentially activated in BRAF-mutated-melanoma cells and a pathway pattern that predicts resistance of BRAF-mutated melanoma to BRAF/MEK inhibitors, providing novel clinical implications for melanoma therapy. In one embodiment, a method comprises (a) testing a sample oiBRAF-mutated melanoma cells isolated from a patient and measuring the expression levels of genes expressed in the following oncogenic pathways: TNFa, EGFR, IFNa, hypoxia, IFNy, STAT3 and Myc; (b) calculating a 7-pathway activation pattern based on the measured expression levels of step (a); and (c) identifying the patient's resistance level to BRAF/MEK inhibitor treatment based on comparison of the calculated 7-pathway activation pattern to a reference.

The invention relates to a method of determining an increased risk of cancer in an immunosuppressed patient, the method comprising: (a) determining the percentage of CD8+CD57+ T-cells in a population of CD8+ T-cells in a sample from the patient; wherein a percentage of 40% or greater of CD8+CD57+ T-cells is indicative of an increased risk of cancer; and/or (b) determining the percentage of CD4+CD57+ T-cells in a population of CD4+ T-cells in a sample from the patient; wherein a percentage of 10% or greater of CD4+CD57+ T-cells is indicative of an increased risk of cancer.

Pharmaceutical compositions for the treatment of cancer are provided. In one embodiment the composition comprises Gamitrinib and a MAPK inhibitor selected from the MAPK inhibitor is selected from RAF265, AZD6244, PLX4720, PD0325901, LGX818, MEK162, vemurafenib, trametinib and dabrafenib. Methods of treating cancer are also provided.

The invention pertains to a method of treating melanoma by administering to a subject in need thereof, a composition comprising a therapeutically effective amount of an inhibitor of PKC-ζ and/or PKC-.Math.. Non-limiting examples of an inhibitor of PKC-ζ and/or PKC-.Math. include ICA-1 and ACPD. The invention also provides PKC-ζ and/or PKC-.Math. as biomarkers for identifying a melanoma in a subject as likely to be responsive or non-responsive to a therapy using an inhibitor of PKC-ζ and/or PKC-.Math.. Accordingly, a method of identifying a subject having a melanoma as being responsive or non-responsive to a melanoma therapy with an inhibitor of PKC-ζ and/or PKC-.Math. based on the levels and/or activity of PKC-ζ and/or and/or PKC-.Math. mRNA or protein in the melanoma cells from the subject are also provided.

This disclosure relates to methods of assaying and scoring PD-L1 expression in tumors. Tumor samples are labeled with an antibody or antibody fragment that specifically binds to human PD-L1 and binding is detected. Binding intensity is compared to background, and tumor cells having membrane staining above background are counted. The percentage of tumor cells containing membrane staining of PD-L1 is determined and the tumor is classified as “PD-L1 positive” if the percentage of tumor cells falls above a predefined level.

The present invention relates to methods for treating melanoma with apilimod and related compositions and methods.

The present invention relates to methods for predicting the probability of a treatment response of a human cancer patient to an immune checkpoint blocker treatment e.g. with anti PD-1, and to methods for predicting the probability of survival of a human cancer patient following an immune checkpoint blocker treatment, and to apparatuses and kits which can be used in these methods.

The present invention relates to methods for the diagnosis and treatment of melanoma. In particular, the invention relates to methods for the diagnosis and treatment of early stage melanoma by measuring the expression of one or more autoantibodies selected from the group consisting of anti-ZBTB7B, anti-PRKCH, anti-TP53, anti-PCTK1, anti-PQBP1, anti-UBE2V1, anti-IRF4, anti-MAPK8_tv2, anti-MSN and anti-TPM1. Further, the present invention relates to kits comprising one or more reagents and/or devices when used in performing the methods for the diagnosis and treatment of melanoma.