Abstract: Human clinical use of a chimeric poliovirus construct has demonstrated excellent anti-tumor effect. Combination with immune checkpoint inhibitors increases the anti-tumor effect. Tumors of different types are susceptible to the combination treatment, including but not limited to melanoma, glioglastoma, renal cell carcinoma, prostate cancer, breast cancer, lung cancer, medulloblastoma, and colorectal cancer.

Abstract: We tested the in vitro and in vivo efficacy of a recombinant bispecific immunotoxin that recognizes both EGFRwt and tumor-specific EGFRvIII receptors. A single chain antibody was cloned from a hybridoma and fused to toxin, carrying a C-terminal peptide which increases retention within cells. The binding affinity and specificity of the recombinant bispecific immunotoxin for the EGFRwt and the EGFRvIII proteins was measured. In vitro cytotoxicity was measured. In vivo activity of the recombinant bispecific immunotoxin was evaluated in subcutaneous models and compared to that of an established monospecific immunotoxin. In our preclinical studies, the bispecific recombinant immunotoxin, exhibited significant potential for treating brain tumors.

Abstract: We have constructed a polynucleotide encoding a bispecific antibody engaging molecule which has one arm that specifically engages a tumor cell which expresses the human EGFRvIII mutant protein on its surface, and a second arm that specifically engages T cell activation ligand CD3. The polynucleotide is codon optimized for expression in CHO cells. The subunits of the engaging molecules are organized to achieve greater efficiency. These are therapeutic agents.

Abstract: The concurrent administration of chemotherapy and immunotherapy has been considered a contraindication because of the concern that the induced lymphopenia would ablate therapeutic efficacy of immunotherapy. Temozolomide has been shown to be an effective chemotherapeutic for patients with malignant gliomas and to deprive patients with glioblastoma (GBM) patients of this agent in order to treat with immunotherapy is controversial. Despite conventional dogma, we demonstrate that both chemotherapy and immunotherapy can be delivered concurrently without negating the effects of immunotherapy. In fact, the temozolomide induced lymphopenia may actually be synergistic with a peptide vaccine.

Abstract: Human clinical use of a chimeric poliovirus construct has demonstrated excellent anti-tumor effect. The mechanism of action is believed to involve both viral oncolysis as well as immune recruitment, both of which lead to necrosis in the area of the tumor. No adverse effects have been observed.

Abstract: We found mutations of the R132 residue of isocitrate dehydrogenase 1 (IDH1) in the majority of grade II and III astrocytomas and oligodendrogliomas as well as in glioblastomas that develop from these lower grade lesions. Those tumors without mutations in IDH1 often had mutations at the analogous R172 residue of the closely related IDH2 gene. These findings have important implications for the pathogenesis and diagnosis of malignant gliomas.

Abstract: We tested the in vitro and in vivo efficacy of a recombinant bispecific immunotoxin that recognizes both EGFRwt and tumor-specific EGFRvIII receptors. A single chain antibody was cloned from a hybridoma and fused to toxin, carrying a C-terminal peptide which increases retention within cells. The binding affinity and specificity of the recombinant bispecific immunotoxin for the EGFRwt and the EGFRvIII proteins was measured. In vitro cytotoxicity was measured. In vivo activity of the recombinant bispecific immunotoxin was evaluated in subcutaneous models and compared to that of an established monospecific immunotoxin. In our preclinical studies, the bispecific recombinant immunotoxin, exhibited significant potential for treating brain tumors.

Abstract: The concurrent administration of chemotherapy and immunotherapy has been considered a contraindication because of the concern that the induced lymphopenia would ablate therapeutic efficacy of immunotherapy. Temozolomide has been shown to be an effective chemotherapeutic for patients with malignant gliomas and to deprive patients with glioblastoma (GBM) patients of this agent in order to treat with immunotherapy is controversial. Despite conventional dogma, we demonstrate that both chemotherapy and immunotherapy can be delivered concurrently without negating the effects of immunotherapy, hi fact, the temozolomide induced lymphopenia may actually be synergistic with a peptide vaccine.

Abstract: We have constructed a polynucleotide encoding a bispecific antibody engaging molecule which has one arm that specifically engages a tumor cell which expresses the human EGFRvIII mutant protein on its surface, and a second arm that specifically engages T cell activation ligand CD3. The polynucleotide is codon optimized for expression in CHO cells. The subunits of the engaging molecules are organized to achieve greater efficiency. These are promising therapeutic agents.

Abstract: Human clinical use of a chimeric poliovirus construct has demonstrated excellent anti-tumor effect. The mechanism of action is believed to involve both viral oncolysis as well as immune recruitment, both of which lead to necrosis in the area of the tumor. No adverse effects have been observed.

Abstract: Human antibody fragments against chrondroitin sulfate proteoglycan 4 can be used to deliver cytotoxic agents to cells which express CSPG4. The agents can be diagnostic or therapeutic moieties. They may be linked by covalent or non-covalent linkages to the antibody fragments. They may be produced as a genetic fusion product or joined together synthetically, for example. When the human antibody fragments are internalized by the cells to which they bind, they can carry with them the attached agents. Thus toxic agents having intracellular targets have enhanced killing upon internalization.

Abstract: We have constructed bispecific antibody engaging molecules which have one arm that specifically engages a tumor cell which expresses the human EGFRvIII mutant protein on its surface, and a second arm that specifically engages T cell activation ligand CD3. The engaging molecules are highly cytotoxic and antigen-specific.

Abstract: We surveyed 1,230 tumors of 60 different types and found that tumors could be divided into types with low (<15%) and high (?15%) frequencies of TERT promoter mutations. The nine TERT-high tumor types almost always originated in tissues with relatively low rates of self renewal, including melanomas, liposarcomas, hepatocellular carcinomas, urothelial carcinomas, squamous cell carcinomas of the tongue, medulloblastomas, and subtypes of gliomas (including 83% of primary glioblastoma, the most common brain tumor type). TERT and ATRX mutations were mutually exclusive, suggesting that these two genetic mechanisms confer equivalent selective growth advantages. In addition to their implications for understanding the relationship between telomeres and tumorigenesis, TERT mutations provide a biomarker for the early detection of urinary tract and liver tumors and aid in the classification and prognostication of brain tumors.

Abstract: The invention provides high affinity antibodies suitable for forming immunotoxins that inhibit the growth of cells expressing human glycoprotein NMB, including glioblastoma multiforme cells, anaplastic astrocytoma cells, anaplastic oligodendroglioma cells, oligodendroglioma cells, and melanoma cells. The antibodies may be formed in cells transformed with an isolated nucleic acid encoding a polypeptide comprising an antibody heavy chain variable region (“VH”) and an antibody light chain variable region (“VL”). Such nucleic acids are provided.

Abstract: IDH1-mutant cell lines and xenografts (e.g., IDH1R132H heterozygous and IDH1R132H homozygous) are derived from human glioblastoma multiforme (GBM) samples. Methods use said cells and xenografts as tools for determining the impact of IDH1R132H on cancer properties including cellular morphology, tumorigenesis, DNA, apoptosis, and metabolic profiles. Methods also use these cell lines for the screening and identification of candidate therapeutic targets.

Abstract: Detection of human antibodies directed against the tumor-specific protein Epidermal Growth Factor Receptor variant Class III (EGFRvIII) provide information on tumor burden and vaccine response. The methods of the invention permit the specific identification of antibodies that are able to bind to EGFRvIII. The methods are useful in determining the presence of an EGFRvIII-expressing tumor and in detecting immune responses following immunization with EGFRvIII-derived peptide as part of a cancer immunotherapy regimen.

Abstract: An antibody having an antigen binding region capable of binding an epitope located in an extracellular portion of MRP3 and methods of utilizing same are provided. In particular, the invention provides antibodies targeted at a MRP3 antigen present on cells expressing MRP3 and methods useful in detecting or targeting cells expression the MRP3 antigen, as well as kits, nucleic acids, polypeptides, and cells for providing the antibodies.

Abstract: The present invention provides small interfering RNA (siRNA) molecules, compositions containing the molecules, and methods of using the compositions to treat gliomas.

Abstract: The invention provides high affinity antibodies suitable for forming immunotoxins that inhibit the growth of cells expressing human glycoprotein NMB, including glioblastoma multiforme cells, anaplastic astrocytoma cells, anaplastic oligodendroglioma cells, oligodendroglioma cells, and melanoma cells. The antibodies may be formed in cells transformed with an isolated nucleic acid encoding a polypeptide comprising an antibody heavy chain variable region (“VH”) and an antibody light chain variable region (“VL”). Such nucleic acids are provided.

Abstract: The invention provides high affinity antibodies suitable for forming Immunotoxins that inhibit the growth of cells expressing human glycoprotein NMB, including glioblastoma multiform cells, anaplastic astrocytoma cells, anaplastic oligodendroglioma cells, oligodendroglioma cells, and melanoma cells.