Abstract: Blockade of immune checkpoints such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1) shows promise in patients with cancer. Inhibitory antibodies directed at these receptors have been shown to break immune tolerance and promote anti-tumor immunity. These agents work particularly well in patients with a certain category of tumor. Such tumors may be particularly susceptible to treatment because of the multitude of neoantigens which they produce.

Abstract: Blockade of immune checkpoints such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1) shows promise in patients with cancer. Inhibitory antibodies directed at these receptors have been shown to break immune tolerance and promote anti-tumor immunity. These agents work particularly well in patients with a certain category of tumor. Such tumors may be particularly susceptible to treatment because of the multitude of neoantigens which they produce.

Abstract: Cancer therapies that combine epigenetic modulating agent(s) with immune modulating agent(s), which were remarkably identified to provide an improved treatment regimen over single agent therapy, are disclosed. In particular embodiments, the invention provides for improved treatment of NSCLC in patients via administration of exemplary immune modulating agents anti-PD-1 antibody or anti-PD-L1 antibody, which were observed to show enhanced activity in combination with the exemplary epigenetic modulating agent 5-deoxyazacytidine. Further, expression markers of responsive neoplastic cells are also disclosed.

Abstract: Blockade of immune checkpoints such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1) shows promise in patients with cancer. Inhibitory antibodies directed at these receptors have been shown to break immune tolerance and promote anti-tumor immunity. These agents work particularly well in patients with a certain category of tumor. Such tumors may be particularly susceptible to treatment because of the multitude of neoantigens which they produce.

Abstract: Blockade of immune checkpoints such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1) shows promise in patients with cancer. Inhibitory antibodies directed at these receptors have been shown to break immune tolerance and promote anti-tumor immunity. These agents work particularly well in patients with a certain category of tumor. Such tumors may be particularly susceptible to treatment because of the multitude of neoantigens which they produce.

Abstract: PD-L1 expression by tumor cells prior to treatment correlates highly with response to anti-PD-1 and anti-PD-L1 therapy (e.g., nivolumab (Bristol-Myers Squibb), pembrolizumab (Merck)) and anti-PD-L1 monotherapy (MPDL3280A (Genentech/Roche)). Nonetheless, the majority of patients with PD-LI(+) tumors do not respond to PD-1 pathway blockade. Distinct gene profiles associated with differential response to treatment with an anti-PD-1 antibody in patients with PD-L1+ renal cell carcinoma have been identified. In particular, a strong up-regulation of genes involved in metabolic functions and pathways was found in patients not responding to the therapy. Additionally, a down-regulation of genes involved in cellular migration functions was found in the same group of patients (non-responders). Specific biomarkers can be used to stratify responders from non-responders for PD-1 pathway blocking drugs.

Abstract: Cancer therapies that combine epigenetic modulating agent(s) with immune modulating agent(s), which were remarkably identified to provide an improved treatment regimen over single agent therapy, are disclosed. In particular embodiments, the invention provides for improved treatment of NSCLC in patients via administration of exemplary immune modulating agents anti-PD-1 antibody or anti-PD-L1 antibody, which were observed to show enhanced activity in combination with the exemplary epigenetic modulating agent 5-deoxyazacytidine. Further, expression markers of responsive neoplastic cells are also disclosed.

Abstract: We characterized a total of 175 HLA-DR-associated phosphopeptides using sequential affinity isolation, biochemical enrichment, mass spectrometric sequencing and comparative analysis. Many were derived from source proteins which may have roles in cancer development, growth and metastasis. Most were expressed exclusively by either melanomas or transformed B cells, suggesting the potential to define cell type-specific phosphatome “fingerprints”. We generated HLA-DR?1*0101-restricted CD4+ T cells specific for a phospho-MART-1 peptide identified in two melanoma cell lines. These T cells showed specificity for phosphopeptide-pulsed antigen presenting cells as well as for intact melanoma cells. MHC II-restricted phosphopeptides recognizable by human CD4+ T cells are potential targets for cancer immunotherapy.

Abstract: We characterized a total of 175 HLA-DR-associated phosphopeptides using sequential affinity isolation, biochemical enrichment, mass spectrometric sequencing and comparative analysis. Many were derived from source proteins which may have roles in cancer development, growth and metastasis. Most were expressed exclusively by either melanomas or transformed B cells, suggesting the potential to define cell type-specific phosphatome “fingerprints”. We generated HLA-DR?1*0101-restricted CD4+ T cells specific for a phospho-MART-1 peptide identified in two melanoma cell lines. These T cells showed specificity for phosphopeptide-pulsed antigen presenting cells as well as for intact melanoma cells. MHC II-restricted phosphopeptides recognizable by human CD4+ T cells are potential targets for cancer immunotherapy.

Abstract: The present invention provides MHC Class II restricted melanoma antigens recognized by CD4+ T cells. This invention further provides prophylactic and therapeutic applications for the Class II restricted melanoma antigens. In particular, this invention provides tyrosinase Class II restricted melanoma antigens, as well as tyrosinase immunogenic peptides which have been modified to enhance their immunogenicity. These antigens can serve as an immunogens or vaccines to prevent or treat melanoma. In addition a method for isolating Class II restricted melanoma antigens or identifying new Class II restricted melanoma antigens is provided.

Abstract: The present invention relates to immortalized, malignant, human, adult prostate epithelial cell lines or cell lines derived therefrom useful in the diagnosis and treatment of prostate cancer. More particularly, the present invention relates to cloned, immortalized, malignant, human, adult prostate epithelial cell lines and uses of these cell lines for the diagnosis and treatment of cancer. Furthermore, the present invention provides for the characterization of said cell lines through the analysis of specific chromosomal deletions.

Abstract: The invention pertains to a method of treating or protecting against melanoma that comprises (a) obtaining a melanoma cell line that expresses one or more shared immunodominant melanoma antigens, (b) modifying the melanoma cell line to render it capable of producing an increased level of a cytokine relative to the unmodified cell line, and (c) administering the melanoma cell line to a mammalian host that has melanoma or is at risk for developing melanoma. Preferably the melanoma cell line is allogeneic and is not MHC-matched to the host.