Abstract: Methods of deconvolving a feature profile of a physical system are provided herein. The present method may include: optimizing a regression between a) a feature profile of a first plurality of distinct components and b) a reference matrix of feature signatures for a second plurality of distinct components, wherein the feature profile is modeled as a linear combination of the reference matrix, and wherein the optimizing includes solving a set of regression coefficients of the regression, wherein the solution minimizes 1) a linear loss function and 2) an L2-norm penalty function; and estimating the fractional representation of one or more distinct components among the second plurality of distinct components present in the sample based on the set of regression coefficients. Systems and computer readable media for performing the subject methods are also provided.

Abstract: Methods are provided to enhance the efficacy of antibody therapy directed to tumor cells.

Abstract: Methods for creating a selector of mutated genomic regions and for using the selector set to analyze genetic alterations in a cell-free nucleic acid sample are provided. The methods can be used to measure tumor-derived nucleic acids in a blood sample from a subject and thus to monitor the progression of disease in the subject. The methods can also be used for cancer screening, cancer diagnosis, cancer prognosis, and cancer therapy designation.

Abstract: Methods of enhancing the efficacy of antibody-directed cellular cytotoxicity (ADCC) for therapy directed to killing of tumor cells are disclosed. Cancer specific cell surface antigens are bound by monoclonal antibodies, thereby stimulating a cytotoxic T cell response characterized by an upregulation of cell surface expression of costimulatory molecules on the T cell. The ADCC response is augmented by the subsequent administration of a second antibody that is an agonist of the costimulatory molecule.

Abstract: Methods are provided for treatment of hematologic cancers, particularly lymphomas and leukemias, including without limitation myelogenous and lymphocytic leukemias. A combination of antibodies specific for CD47; and specific for a cancer associated cell surface marker are administered to the patient, and provide for a synergistic decrease in cancer cell burden. The combination of antibodies may comprise a plurality of monospecific antibodies, or a bispecific or multispecific antibody. Markers of interest include without limitation, CD20, CD22, CD52, CD33; CD96; CD44; CD123; CD97; CD99; PTHR2; and HAVCR2.

Abstract: Methods for creating a library of recurrently mutated genomic regions and for using the library to analyze cancer-specific and patient-specific genetic alterations in a patient are provided. The methods can be used to measure tumor-derived nucleic acids in patient blood and thus to monitor the progression of disease. The methods can also be used for cancer screening.

Abstract: Predictive biomarkers identify those patients suffering from immunoglobulin positive (Ig+) B lineage malignancies that are responsive to active immunotherapy, where the active immunotherapy comprises vaccination with a tumor-specific idiotype-immunogen. It is shown herein that patient responsiveness to the idiotype-immunogen is dependent upon the sequence of the immunogen, where an immunogen having a low number of tyrosine residues in the CDR1 (herein termed CDR1-Y10) regions of one or both of the immunogen heavy and light chains is predictive of a positive anti-tumor response, while a high number of CDR1 tyrosine residues (herein termed CDR1-Yhi) is predictive of a low anti tumor response.

Abstract: Methods are provided for treatment of hematologic cancers, particularly lymphomas and leukemias, including without limitation myelogenous and lymphocytic leukemias. A combination of antibodies specific for CD47; and specific for a cancer associated cell surface marker are administered to the patient, and provide for a synergistic decrease in cancer cell burden. The combination of antibodies may comprise a plurality of monospecific antibodies, or a bispecific or multispecific antibody. Markers of interest include without limitation, CD20, CD22, CD52, CD33; CD96; CD44; CD123; CD97; CD99; PTHR2; and HAVCR2.

Abstract: Methods, compositions, and kits are provided for providing a diagnosis, a prognosis, or a prediction of responsiveness to a therapy for a patient with a hematological malignancy. In practicing the subject methods, the expression level of at least one leukemia stem cell (LSC) genes in a tissue sample is assayed to obtain an LSC expression representation. The LSC expression representation is then employed to determine if an individual has a hematological malignancy, to provide a prognosis to a patient with a hematological malignancy, and/or to provide a prediction of the responsiveness of a patient with a hematological malignancy to a therapy. Also provided are screening methods for identifying novel therapies for patients with a hematological malignancy, and compositions and kits for use in these screening methods.

Abstract: Methods of enhancing the efficacy of antibody-directed cellular cytotoxicity (ADCC) for therapy directed to killing of tumor cells are disclosed. Cancer specific cell surface antigens are bound by monoclonal antibodies, thereby stimulating a cytotoxic T cell response characterized by an upregulation of cell surface expression of costimulatory molecules on the T cell. The ADCC response is augmented by the subsequent administration of a second antibody that is an agonist of the costimulatory molecule.

Abstract: Methods are provided for treatment of hematologic cancers, particularly lymphomas and leukemias, including without limitation myelogenous and lymphocytic leukemias. A combination of antibodies specific for CD47; and specific for a cancer associated cell surface marker are administered to the patient, and provide for a synergistic decrease in cancer cell burden. The combination of antibodies may comprise a plurality of monospecific antibodies, or a bispecific or multispecific antibody. Markers of interest include without limitation, CD20, CD22, CD52, CD33; CD96; CD44; CD123; CD97; CD99; PTHR2; and HAVCR2.

Abstract: Measurement of a single gene expressed by tumor cells (LMO2) and a single gene expressed by the immune microenvironment (TNFRSF9), which determination may be referred to herein as a two gene score (TGS), powerfully predicts overall survival in patients with NHL, particularly overall survival in the context of anthracycline-based chemotherapy or co-treatment with anthracycline-based chemotherapy and anti-CD20 immunotherapy. It is shown herein that increased levels of LMO2 and TNFRSF9 correlate with a positive patient response and improved prognosis.