Abstract: Described are compositions and methods relating to immune cells which express both a chimeric antigen receptor which binds to the IL13 receptor ?-2 (IL13R?2) and a O6-methylguanine DNA methyltransferase (MGMT) protein. Viral particles containing an IL13 chimeric antigen receptor (IL13CAR) or variant thereof and an MGMT protein or variant thereof are used to transfect immune cells such as T cells, imparting to the transfected cells both IL13R?2-targeting activity and resistance to the chemotherapeutic agent temozolomide (TMZ). The compositions and methods described are useful for cancer therapy such as the treatment of a high-grade malignant glioma.

Abstract: The present invention relates to compositions and methods for creation of vector nucleic acid sequences (e.g., retroviral nucleic acid sequences) that comprise two or more exogenous nucleic acid sequences that encode highly homologous (e.g., identical) polypeptide sequences, yet wherein at least one of the exogenous nucleic acid sequences has been mutated using degenerate codons for purpose of reducing homology between the two or more exogenous nucleic acid sequences while maintaining the encoded polypeptide sequence. Preferred nucleic acid sequences include those encoding multi-chimeric immune receptor (CIR) genes. Specific nucleic acid sequences of such CIR genes are also disclosed.

Abstract: This invention provides a method for increasing apoptosis in a cancer cell comprising contacting the cancer cell with (a) gemcitabine and (b) C6-ceramide, sequentially or concomitantly, wherein the gemcitabine and C6-ceramide are in amounts such that the apoptosis induced by the combination of gemcitabine and C6-ceramide is greater than the apoptosis induced by contacting the cancer cell with either gemcitabine alone or C6-ceramide alone. This invention also provides a method of decreasing the size of a tumor, which method comprises contacting the tumor with (a) gemcitabine and (b) C6-ceramide, sequentially or concomitantly, wherein the gemcitabine and C6-ceramide are in amounts such that the decrease in tumor size induced by the combination of gemcitabine and C6-ceramide is greater than the decrease in tumor size induced by contacting the tumor with either gemcitabine alone or C6-ceramide alone.

Abstract: This invention provides methods for determining whether a breast, prostate or ovarian tumor or tumor cell is aggressive, based on the quantitative measurement of p66-Shc and phosphorylated Shc. This invention also provides related methods of determining the likelihood of tumor recurrence. This invention further provides a method for determining whether a tumor can be successfully treated using a tyrosine kinase inhibitor. Finally, this invention provides antibodies and kits for practicing the instant methods.

Abstract: This invention provides a method for increasing apoptosis in tumor cells and a method of decreasing a size of a tumor, said methods comprising contacting the tumor cells with: a) an effective amount of at least one antitumor chemotherapeutic agent and b) an effective amount of a ceramide, sequentially or concomitantly, wherein the apoptosis induced by the combination of the antitumor chemotherapeutic agent and the ceramide is greater than the apoptosis induced by contact of the tumor cells with either the antitumor chemotherapeutic agent alone or the ceramide alone. This invention also provides a method of treating cancer in a subject which comprises a method according to either of the above-described methods. This invention provides a method for treating cancer in a subject comprising administering to the subject an effective amount of at least one antitumor chemotherapeutic agent and an effective amount of at least one ceramide, sequentially or concomitantly.

Abstract: Bone marrow cells have been demonstrated to be useful in the maintenance of pancreatic islet ? cell viability, structure, and/or function in culture for a sustained period. Bone marrow cells were also found to promote ? cell growth while reducing inflammatory cytokine release and reduce apoptosis. Moreover, islet cells co-cultured with bone marrow cells were shown to retain insulin response function and to function in an islet cell transplant in a mouse model of diabetes to restore normal insulin secretion. Cord blood cells and isolated peripheral CD34+ blood cells were unable to support ? islet cell growth or increase survival.

Abstract: This invention provides compositions of matter, articles of manufacture and methods for delivering and/or affixing a stem cell to a target tissue. This invention also provides related nucleic acids, vectors, cell, methods of production, and kits.

Abstract: The present invention provides a method for predicting whether an individual (e.g., patient) will benefit from a (one or more) treatment for cancer comprising determining the amount of p66-Shc present in cancerous cells or precancerous cells (e.g., displasia) of the individual. If the amount of p66-Shc present in the cells of the individual is lower than the amount of p66-Shc in a control, then the individual will likely benefit from the treatment.

Abstract: The invention provides a method of modulating blood glucose levels by treating or preventing pancreas-related disorders with thyrotropin-releasing hormone (TRH) or a TRH derivative. Diabetes mellitus, pancreatic islet destruction, pancreatic beta cell malfunction, and hyperglycemia-related malfunction are preferably treated or prevented.

Abstract: This invention provides methods for treating a subject afflicted with a proliferative disorder comprising administering to the subject a therapeutically effective amount of an agent which inhibits the expression of p46 Shc and/or p52 Shc, inhibits the activity of p46 Shc and/or p52 Shc in the subject, or increases the level of phosphorylated p66 Shc in the subject. This invention also provides methods for determining whether an agent inhibits the phosphorylation of p46 Shc or p52 Shc; inhibits the dephosphorylation of p66 Shc comprising; or an agent inhibits the binding of a Shc A protein with a protein to which the Shc A protein must bind in a cell in order to carry out its proliferative function. This invention also provides articles of manufacture for use in treating a proliferative disorder in a subject.

Abstract: This invention provides a method for increasing apoptosis in tumor cells and a method of decreasing a size of a tumor, said methods comprising contacting the tumor cells with: a) an effective amount of at least one antitumor chemotherapeutic agent and b) an effective amount of a ceramide, sequentially or concomitantly, wherein the apoptosis induced by the combination of the antitumor chemotherapeutic agent and the ceramide is greater than the apoptosis induced by contact of the tumor cells with either the antitumor chemotherapeutic agent alone or the ceramide alone. This invention also provides a method of treating cancer in a subject which comprises a method according to either of the above-described methods. This invention provides a method for treating cancer in a subject comprising administering to the subject an effective amount of at least one antitumor chemotherapeutic agent and an effective amount of at least one ceramide, sequentially or concomitantly.

Abstract: The arming of activated T cells (ATC) with BiAbs can overcome major barriers for successful adoptive immunotherapy. The BiAb approach takes the advantage of the targeting specificity of monoclonal antibodies and the cytotoxic capacity of T cells to lyse tumors. Arming of ATC with BiAb makes every T cell an antigen-specific CTL and infusions of such cells will markedly increase the effective precursor frequency of CTL in the cancer patient. Furthermore, the ability of such armed ATC to kill multiple times without rearming with BiAb, secrete tumoricidal cytokines, secrete chemokines, and survive in patients for up to 8 days after the last infusion or in Beige/SCID mice for over 13 weeks after cessation of treatment. The persistence of cells in the Beige/SCID after infusion show long-term survival capability in the host.

Abstract: The present invention relates to recombinant mycobacteria, particularly recombinant M. bovis, BCG, engineered to express a MUC1 polypeptide and human interleukin-2 for use in cancer immunotherapy.

Abstract: Methods and kits for diagnosing the presence of and prognosing the of stages of HIV disease, involving correlating rate of CD4% decline, CMC activity and plasma HIV RNA load, are disclosed. In particular, the methods and kits pertain to diagnosis and prognosis of disease progression in retroviral infections.