Abstract: Provided is a combination and a method of using combination therapy to treat tumor in an individual. An immunotoxin and an immunostimulator are administered to the individual, wherein the immunotoxin comprises a single chain variable region antibody fused to a PE38 truncated Pseudomonas exotoxin, and the immunostimulator comprises an anti-CD40 agonist antibody. The combination may further comprise a checkpoint inhibitor comprising one or more of an anti-PD-1 antibody and an anti-PD-L1 antibody.

Abstract: Provided is a method of treating a distal tumor in an individual by administering a chimeric poliovirus to a first tumor in an effective amount to induce an antitumor immune response effective to treat a distal tumor.

Abstract: Methods of testing tumor samples for mutational burden and/or for expression profiles permit the prediction of responsiveness of an individual to immunotherapy comprising PVSRIPO. Those predicted to respond are treated with PVSRIPO and those predicted not to respond are treated with other agents.

Abstract: Chimeric poliovirus is capable of activating antigen presenting cells. The activation of the antigen presenting cells may be in vitro, ex vivo, or in vivo. The activated antigen presenting cells may be administered alone or with an antigen or vaccine. The activated antigen may be loaded in vitro or ex vivo with antigen to form antigen-loaded, activated, antigen presenting cells. These may be administered therapeutically. Therapeutic administration of antigen presenting cells may be used as an adjuvant to other therapies.

Abstract: We determined the sequence of ATRX and DAXX in 447 cancers from various sites. We found mutations most commonly in pediatric glioblastoma multiformae (GBM) (11.1%), adult GBM (6.5%), oligodendrogliomas (7.7%) and medulloblastomas (1.5%); and showed that Alternative Lengthening of Telomeres (ALT), a telomerase-independent telomere maintenance mechanism found in cancers that have not activated telomerase, perfectly correlated with somatic mutations of either gene. In contrast, neuroblastomas, and adenocarcinomas of the ovary, breast, and pancreas were negative for mutations in ATRX and DAXX. Alterations in ATRX or DAXX define a specific molecular pathway that is closely associated with an alternative telomere maintenance function in human cancers.

Abstract: Regional, tumor-targeted, cytotoxic therapy, such as D2C7-immunotoxin (D2C7-IT), not only specifically target and destroy tumor cells, but in the process initiate immune events that promote an in situ vaccine effect. The antitumor effects are amplified by immune checkpoint blockade which engenders a long-term systemic immune response that effectively eliminates all tumor cells.

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 gliblastomas 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: Regional, tumor-targeted, cytotoxic therapy, such as D2C7-immunotoxin (D2C7-IT), not only specifically target and destroy tumor cells, but in the process initiate immune events that promote an in situ vaccine effect. The antitumor effects are amplified by immune checkpoint blockade which engenders a long-term systemic immune response that effectively eliminates all tumor cells.

Abstract: Provided is a method of treating a tumor in an individual by neoadjuvant therapy, wherein the individual has not previously undergone a resection of the tumor, the method comprising administering an immunotoxin alone or an immune checkpoint inhibitor and an immunotoxin, such as D2C7-immunotoxin (D2C7-IT), followed by resection of the tumor. The method may further comprise administration of immune checkpoint inhibitor following resection.

Abstract: Provided is a method of treating a tumor in an individual by neoadjuvant therapy, wherein the individual has not previously undergone treatment to effectively reduce tumor burden, the method comprising administering an oncolytic chimeric poliovirus construct, or an oncolytic chimeric poliovirus construct and an immune checkpoint inhibitor, followed by reduction of the tumor. The method may further comprise administration of immune checkpoint inhibitor or oncolytic chimeric poliovirus construct following reduction of tumor. Kits for performing the methods are also provided.

Abstract: Methods of testing tumor samples for mutational burden and/or for expression profiles permit the prediction of responsiveness of an individual to immunotherapy comprising PVSRIPO. Those predicted to respond are treated with PVSRIPO and those predicted not to respond are treated with other agents.

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 gliblastomas 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 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 gliblastomas 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: Methods that rapidly, sensitively, and specifically detect mutations in IDH1/2 and the TERT promoter employ amplification of particular portions of the genes that experience frequent and exquisitely localized mutations. The ability to distinguish between sequences that differ only by one nucleotide and which may be present in very low ratios is essential for such an assay.

Abstract: Oligodendrogliomas are the second most common malignant brain tumor in adults. These tumors often contain a chromosomal abnormality involving a pericentromeric fusion of chromosomes 1 and 19, resulting in losses of the entire short arm of the former and the long arm of the latter. To identify the molecular genetic basis for this alteration, we performed exomic sequencing of seven anaplastic oligodendrogliomas with chromosome 1p and 19q losses. Among other changes, we found that that CIC (homolog of the Drosophila gene capicua) on chromosome 19q was somatically mutated in six of the seven cases and that FUBP1 (far upstream element (FUSE) binding protein) on chromosome 1p was somatically mutated in two of the seven cases. Examination of 27 additional oligodendrogliomas revealed 12 and 3 more tumors with mutations of CIC and FUBP1, respectively, 58% of which were predicted to result in truncations of the encoded proteins.

Abstract: Chimeric poliovirus is capable of activating antigen presenting cells. The activation of the antigen presenting cells may be in vitro, ex vivo, or in vivo. The activated antigen presenting cells may be administered alone or with an antigen or vaccine. The activated antigen may be loaded in vitro or ex vivo with antigen to form antigen-loaded, activated, antigen presenting cells. These may be administered therapeutically. Therapeutic administration of antigen presenting cells may be used as an adjuvant to other therapies.

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 gliblastomas 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 determined the sequence of ATRX and DAXX in 447 cancers from various sites. We found mutations most commonly in pediatric glioblastoma multiformae (GBM) (11.1%), adult GBM (6.5%), oligodendrogliomas (7.7%) and medulloblastomas (1.5%); and showed that Alternative Lengthening of Telomeres (ALT), a telomerase-independent telomere maintenance mechanism found in cancers that have not activated telomerase, perfectly correlated with somatic mutations of either gene. In contrast, neuroblastomas, and adenocarcinomas of the ovary, breast, and pancreas were negative for mutations in ATRX and DAXX. Alterations in ATRX or DAXX define a specific molecular pathway that is closely associated with an alternative telomere maintenance function in human cancers.

Abstract: Regional, tumor-targeted, cytotoxic therapy, such as D2C7-immunotoxin (D2C7-IT), not only specifically target and destroy tumor cells, but in the process initiate immune events that promote an in situ vaccine effect. The antitumor effects are amplified by immune checkpoint blockade which engenders a long-term systemic immune response that effectively eliminates all tumor cells.

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 gliblastomas 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.