Abstract: Resistance of randomly dispersed and oxygen-starved lung tumor cells to chemo- and radiotherapy constitutes the vast majority recurrences and death from lung cancer. We use sickle cells derived from humans with sickle cell anemia to target oxygen-deprived tumor cells that persist and multiply after conventional treatment. Transfused sickle cells selectively occluded tumor microvessels and shut down blood flow to these oxygen-deprived pockets leading to tumor cell death and complete shrinkage of aggressive lung tumors. Combining the sickle cells with a vascular disrupting agents and radiation injure and narrow tumor blood vessels, amplified the scale of sickle cell-induced blood vessel closure and tumor cell killing. The strength of the tumor killing produced by this combination exceeded that of either agent alone or combined with conventional anti-angiogenics, chemotherapy or radiation.

Abstract: Amid their enormous biologic diversity, we have discovered a new group of evolutionarily modified SAgs, SEG-SEI, that in partnership with endogenous SEG-SEI retain the ability to generate anti-tumor T effector cell devoid of the cytokine-mediated toxicity. Such toxicity has hampered the effective use of canonical SAgs for human cancer treatment. For their MHCII partner, we selected the human HLA-DQ8 allele and show that its contact with SEG-SEI is obligatory for the anti-tumor effect. Here we further show that SEG-SEI collaborate with HLA-DQ8 alleles to expand, differentiate, and chemotactically recruit a tumor neoantigen-primed tumor reactive T cell population that propagates both an acute tumoricidal response and long-term T-cell memory/survival.

Abstract: Resistance of randomly dispersed and oxygen-starved lung tumor cells to chemo- and radiotherapy constitutes the vast majority recurrences and death from lung cancer. We use sickle cells derived from humans with sickle cell anemia to target oxygen-deprived tumor cells that persist and multiply after conventional treatment. Transfused sickle cells selectively occluded tumor microvessels and shut down blood flow to these oxygen-deprived pockets leading to tumor cell death and complete shrinkage of aggressive lung tumors. Combining the sickle cells with a vascular disrupting agents and radiation injure and narrow tumor blood vessels, amplified the scale of sickle cell-induced blood vessel closure and tumor cell killing. The strength of the tumor killing produced by this combination exceeded that of either agent alone or combined with conventional anti-angiogenics, chemotherapy or radiation.

Abstract: Here we show that SEG/SEI presented from a HLA-DQ8 (HLA-DQB*0302 and HLA-DQA*0301) platform prevent the de novo outgrowth (vaccination) of Lewis lung carcinoma (LLC) and B16-F10 melanoma and retard the growth of established tumors with no significant toxicity. Vaccination of DQ8 tg mice with irradiated LLC or B16-F10 melanoma followed by SEG/SEI immunization and live tumor challenge resulted in 100 and 66% survival respectively for 200 days compared to a median survival of 20 days for untreated controls (p<0.001). In vaccination studies, DQ8 tg mice showed a surge in IFN? serum levels reaching 3000 fold above baseline devoid of a parallel spike in TNF? levels above baseline levels. Presentation of the SEG/SEI superantigen from a MHC-DQ8 platform, therefore, augments the therapeutic index of these SAgs inducing a tumoricidal response against Lewis lung carcinoma and B16 melanoma accompanied by a sharp increase of therapeutic IFN? levels absent toxic levels of TNF?.

Abstract: Here we show that SEG/SEI presented from a HLA-DQ8 (HLA-DQB*0302 and HLA-DQA*0301) platform prevent the de novo outgrowth (vaccination) of Lewis lung carcinoma (LLC) and B16-F10 melanoma and retard the growth of established tumors with no significant toxicity. Vaccination of DQ8 tg mice with irradiated LLC or B16-F10 melanoma followed by SEG/SEI immunization and live tumor challenge resulted in 100 and 66% survival respectively for 200 days compared to a median survival of 20 days for untreated controls (p<0.001). In vaccination studies, DQ8 tg mice showed a surge in IFN? serum levels reaching 3000 fold above baseline devoid of a parallel spike in TNF? levels above baseline levels. Presentation of the SEG/SEI superantigen from a MHC-DQ8 platform, therefore, augments the therapeutic index of these SAgs inducing a tumoricidal response against Lewis lung carcinoma and B16 melanoma accompanied by a sharp increase of therapeutic IFN? levels absent toxic levels of TNF?.

Abstract: The present invention provides therapeutic mammalian cells which synthesize and express SS hemoglobin and a tumoricidal transgene. They are produced by transduction of SS erythroid progenitors/erythroblasts using viral vectors comprising a tumoricidal transgene operatively linked to the coding region of SS ?-globin promoter/enhancer. Such transduced SS erythroid cells differentiate into mature SSRBCs that exhibit sustained synthesis and expression of SS hemoglobin, a tumoricidal protein(s). Both mature and progenitor SS-cells carrying tumoricidal transgene(s) are capable of selectively localizing in tumor microenvironment, occluding tumor microvessels and inducing a tumoricidal response.

Abstract: The present invention contemplates a method of treating cancer comprising CD47 deficient sickle cell erythroid precursors/progenitors or hematopoietic stem cells transduced with viral altered genomic DNA from normal or tumor bearing hosts and used to polarize macrophages and/or activate a cytotoxic T cell tumoricidal response.

Abstract: The present invention provides therapeutic mammalian cells which synthesize and express SS hemoglobin and a tumoricidal transgene. They are produced by transduction of SS erythroid progenitors/erythroblasts using viral vectors comprising a tumoricidal transgene operatively linked to the coding region of SS ?-globin promoter/enhancer. Such transduced SS erythroid cells differentiate into mature SSRBCs that exhibit sustained synthesis and expression of SS hemoglobin, a tumoricidal protein(s). Both mature and progenitor SS-cells carrying tumoricidal transgene(s) are capable of selectively localizing in tumor microenvironment, occluding tumor microvessels and inducing a tumoricidal response.

Abstract: The present invention comprises the use of sickle cells or sickle cell precursors loaded with a therapeutic agent that localize in tumors and induce a tumoricidal response.

Abstract: The present invention contemplates therapeutic constructs comprising wild type SEG superantigen, its homologues and tumor targeting fusion proteins devoid of neutralizing antibodies in human sera for treatment of cancer

Abstract: The present invention comprises the use of sickle cells or sickle cell precursors loaded with a therapeutic agent that localize in tumors and induce a tumoricidal response.

Abstract: Described herein is an interactive digital software program and hardware that enables rapid acquisition of textual or audio subject matter, its conversion to editable text and immediate compression into a user understandable summary. The software program maximizes “time on task” while minimizing the time-consuming steps of “concept capture” and “compression”. The instant invention provides an accurate condensate of textual subject matter in a fraction of the time it would take to prepare such a document by manual note taking. In a single step, mobile devices such as cameras, camera phones, tablets, iPODs™, scanners and the like rapidly capture textual images convert them to OCR and to a user understandable summary in a fraction of the time it takes to process such a document by manual note taking. With more study time available for repetitious practice of the lesson, the user improves preparedness and performance on tests and presentations.

Abstract: The present invention provides erythrocytes or nucleated erythrocyte precursors from animals or patients with at least one S hemoglobin allele which are capable of selectively localizing in tumor vasculature resulting in vaso-occlusion, hemolysis and heme release. A tumoricidal effect is achieved when these cells are administered in before during or after administration of (i) an agent(s) that interferes with degradation of reactive oxygen species, (ii) impairs glucose uptake and/or (iii) chemotherapy. These cells also carry oncolytic viruses, antitumor proteins, multidrug resistant proteins, chemotherapy, monoclonal antibodies, superantigens, superantigen conjugates and fusion proteins, siRNAs, plasmids and non-protein toxins and attenuated tumoricidal bacterial cells specifically into the tumors and induce a tumoricidal effect.

Abstract: Described herein is an interactive digital software program and hardware that enables rapid acquisition of textual or audio subject matter, its conversion to editable text and immediate compression into a user understandable summary. The software program maximizes “time on task” while minimizing the time-consuming steps of “concept capture” and “compression”. The instant invention provides an accurate condensate of textual subject matter in a fraction of the time it would take to prepare such a document by manual note taking. In a single step, mobile devices such as cameras, cameraphones, tablets, iPODs, scanners and the like rapidly capture textual images convert them to OCR and to a user understandable summary in a fraction of the time it takes to process such a document by manual note taking. With more study time available for repetitious practice of the lesson, the user improves preparedness and performance on tests and presentations.

Abstract: The present invention provides erythrocytes or nucleated erythrocyte precursors from animals or patients with at least one S hemoglobin allele which are capable of selectively localizing in tumor vasculature resulting in vaso-occlusion, hemolysis and heme release. A tumoricidal effect is achieved when these cells are administered in before during or after administration of (i) an agent(s) that interferes with degradation of reactive oxygen species, (ii) impairs glucose uptake and/or (iii) chemotherapy. These cells also carry oncolytic viruses, antitumor proteins, multidrug resistant proteins, chemotherapy, monoclonal antibodies, superantigens, superantigen conjugates and fusion proteins, siRNAs, plasmids and non-protein toxins and attenuated tumoricidal bacterial cells specifically into the tumors and induce a tumoricidal effect.

Abstract: The present invention contemplates therapeutic constructs comprising superantigen homologues devoid of neutralizing antibodies in human sera conjugated recombinantly to costimulatory and tumor targeting molecules for treatment of cancer

Abstract: The presence of tumor nodules in organs often results in serious clinical manifestations and the permeation by cancer cells of sheaths surrounding organs often produces clinical manifestations of pleural effusion, ascites or cerebral edema. The present invention addresses this problem by providing a method for treating minors comprising (a) intratumoral administration of a superantigen and/or (b) intrathecal or intracavitary administration of a superantigen directly into the sheath. Intratumoral superantigen results in significant and sustained reduction of the tumor size. Intrathecal administration produces significant sustained reduction of the fluid accumulation associated with clinical improvement and prolonged survival. Useful superantigen compositions for intrathecal and intratumoral injection include tumoricidally effective homologues, fragments and fusion proteins of native superantigens.

Abstract: The present invention comprises compositions and methods for treating a tumor or neoplastic disease in a host, The methods employ conjugates comprising superantigen polypeptides or nucleic acids with other structures that preferentially bind to tumor cells and are capable of inducing apoptosis. Also provided are superantigen-glycolipid conjugates and vesicles that are loaded onto antigen presenting cells to activate both T cells and NKT cells. Cell-based vaccines comprise tumor cells engineered to express a superantigen along with glycolipids products which, when expressed, render the cells capable of eliciting an effective anti-tumor immune response in a mammal into which these cells are introduced. Included among these compositions are tumor cells, hybrid cells of tumor cells and accessory cells, preferably dendritic cells. Also provided are T cells and NKT cells activated by the above compositions that can be administered for adoptive immunotherapy.

Abstract: The present invention comprises the use of sickle cells or sickle cell precursors loaded with a therapeutic agent that localizes in tumors and induces a tumoricidal response.

Abstract: The presence of tumor nodules in organs often results in serious clinical manifestations and the permeation by cancer cells of sheaths surrounding organs often produces clinical manifestations of pleural effusion, ascites or cerebral edema. The present invention addresses this problem by providing a method for treating tumors comprising (a) intratumoral administration of a superantigen and/or (b) intrathecal or intracavitary administration of a superantigen directly into the sheath. Intratumoral superantigen results in significant and sustained reduction of the tumor size. Intrathecal administration produces significant sustained reduction of the fluid accumulation associated with clinical improvement and prolonged survival. Useful superantigen compositions for intrathecal and intratumoral injection include tumoricidally effective homologues, fragments and fusion proteins of native superantigens.