Abstract: Antibodies that penetrate cell nuclei and inhibit DNA repair or interfere with DNA metabolism are provided for treatment of cancer (both directly and by sensitizing cancer cells to DNA-damaging treatments) or inhibiting or preventing viral infection, proliferation or metabolism. The method involves treating cells with a composition containing cell-penetrating anti-DNA antibodies or derivatives thereof, alone or in combination with treatment that induces DNA damage such as DNA-damaging chemotherapy or radiation. The impact of the cell-penetrating anti-DNA antibodies or derivatives thereof is potentiated in cancer cells that are deficient in DNA repair, and the cell-penetrating anti-DNA antibodies or derivatives thereof are synthetically lethal to cancer cells with DNA repair deficiencies.

Abstract: Antigen binding molecules that bind to the epitope of 3E10, and methods of use thereof are provided. The antigen binding molecule can include, for example, two or more variant single chain variable fragments (scFv) of monoclonal antibody 3E10, wherein the variant scFv has one or more insertions, deletions, or substitutions relative to a corresponding 3E10 scFv, and wherein the molecule can bind, preferably specifically bind, to the epitope of 3E10. Methods of using the antigen binding molecules for treating cancer and viral infections or preventing viral infections are also provided.

Abstract: The invention provides for a fusion protein comprising a 3E10 Fv joined to a Hsp-70, Hsp-27, Hsp-90 or GRP-78 or portion thereof, and optionally, the 3E10 Fv comprising an amino acid sequence AGIH at its amino terminus.

Abstract: Antibodies that penetrate cell nuclei and inhibit DNA repair or interfere with DNA metabolism are provided for treatment of cancer (both directly and by sensitizing cancer cells to DNA-damaging treatments) or inhibiting or preventing viral infection, proliferation or metabolism. The method involves treating cells with a composition containing cell-penetrating anti-DNA antibodies or derivatives thereof, alone or in combination with treatment that induces DNA damage such as DNA-damaging chemotherapy or radiation. The impact of the cell-penetrating anti-DNA antibodies or derivatives thereof is potentiated in cancer cells that are deficient in DNA repair, and the cell-penetrating anti-DNA antibodies or derivatives thereof are synthetically lethal to cancer cells with DNA repair deficiencies.

Abstract: Provided herein are methods for inducing growth arrest or apoptosis in cancer cells in a subject. Further provided are methods of inhibiting or treating metastasis of a cancer cell in a subject. The methods involve administering to the subject an antibody conjugate containing an antibody, variant thereof, or functional fragment thereof having binding specificity of the antibody as produced by the hybridoma having ATCC accession number PTA 2439 and a biologically active molecule. The antibody (e.g., mAb 3E10) variant or functional fragment thereof provides for the in vivo transduction of the conjugate to the nucleus of mammalian cells, where the conjugated biologically active molecule may exert its effect. In particular embodiments, the antibody conjugate comprises a single chain Fv fragment of an antibody having the binding specificity of mAb 3E10 produced by ATCC PTA 2439, conjugated to p53.

Abstract: It has been established that cancer cells with oncogenic mutants in the small GTPase K-Ras are susceptible to antibodies that bind intracellular guanosine, but delivery of antibodies into cells can be challenging. A subset of lupus autoantibodies is associated with anti-guanosine activity, and is capable of cellular penetration. These antibodies have potential as therapeutic agents targeted towards K-Ras associated malignancies.

Abstract: The invention provides methods for selective targeting of live cells, which have undergone or are undergoing radiation or chemotherapy, at a site of interest with a cell-penetrating polypeptide. In one embodiment of the invention, the method comprises contacting the live cells with a cell-penetrating polypeptide comprising cell-penetrating determinants so that the cell-penetrating polypeptide binds extracellular DNA near or around the live cells so as to form a complex or association therewith such that the complex or associated polypeptide-DNA so bound bind the live cells and penetrates the live cells thereby selectively targeting live cells at a site of interest with a cell-penetrating polypeptide.

Abstract: The invention provides a method for inhibiting an intracellular target in a cell with a bispecific antibody comprising contacting the cell with a bispecific antibody having a first Fv fragment with a cell-penetrating determinant and a second Fv fragment with an intracellular target-binding determinant under suitable conditions so that the first Fv fragment causes the bispecific antibody to enter the cell and the second Fv fragment binds the intracellular target in the cell and thereby inhibiting the intracellular target.

Abstract: The invention provides a method for inhibiting an intracellular target in a cell with a bispecific antibody comprising contacting the cell with a bispecific antibody having a first Fv fragment with a cell-penetrating determinant and a second Fv fragment with an intracellular target-binding determinant under suitable conditions so that the first Fv fragment causes the bispecific antibody to enter the cell and the second Fv fragment binds the intracellular target in the cell and thereby inhibiting the intracellular target.

Abstract: Cancer cells with defects in DNA repair are highly susceptible to DNA-damaging agents, but delivery of therapeutic agents into cell nuclei can be challenging. A sub-set of autoantibodies having nucleolytic activity are capable of nuclear penetration. These antibodies can be used as therapeutic agents targeted towards DNA repair-deficient malignancies.

Abstract: Provided herein are conjugate molecules containing a substrate for a nucleoside transport pathway linked to an active agent, wherein the conjugate can be transported into a cell or into the nucleus of a cell via a cellular nucleoside transport pathway. Further provided are methods of delivering a conjugate molecule to a target cell expressing a nucleoside transport pathway, wherein the conjugate contains a substrate for the nucleoside transport pathway linked to an active agent. Also provided are methods for screening for conjugates that are transported by nucleoside transport pathways. Further provided are methods of treating a patient having a disease or disorder affecting tissues expressing nucleoside transport pathways, in which a conjugate containing an agent effective in treating the disorder is administered to the patient. Also provided are methods of treating a patient having an autoimmune disorder involving administering to the patient a compound that inhibits a nucleoside transport pathway.

Abstract: The present invention provides peptide conjugates having improved solubility as well as increased secretion during cell based production, as well as methods of utilizing such peptides. The peptide conjugates include a short peptide domain defined by the amino acid sequence AGIH (SEQ ID NO: 8) and may include a biologically active molecule useful in intracellular and intranuclear transport of the biologically active molecule to treat various disorders and diseases.

Abstract: The invention provides methods for determining whether a subject is suffering from a rheumatoid arthritis associated with the BRAF oncogene comprising contacting isolated fibroblasts from the subject with a molecule or pool of molecules directed to the BRAF oncogene; and culturing the sample in the presence of the agent and determining whether BRAF oncogene expression by the cell is decreased and/or whether cells in the sample return to a less transformed phenotype, exhibit decreased cell proliferation and/or exhibit increased contact inhibition, any of which is indicative that the subject is suffering from a rheumatoid arthritis associated with the BRAF oncogene.

Abstract: Provided herein are conjugate molecules containing a substrate for a nucleoside transport pathway linked to an active agent, wherein the conjugate can be transported into a cell or into the nucleus of a cell via a cellular nucleoside transport pathway. Further provided are methods of delivering a conjugate molecule to a target cell expressing a nucleoside transport pathway, wherein the conjugate contains a substrate for the nucleoside transport pathway linked to an active agent. Also provided are methods for screening for conjugates that are transported by nucleoside transport pathways. Further provided are methods of treating a patient having a disease or disorder affecting tissues expressing nucleoside transport pathways, in which a conjugate containing an agent effective in treating the disorder is administered to the patient. Also provided are methods of treating a patient having an autoimmune disorder involving administering to the patient a compound that inhibits a nucleoside transport pathway.

Abstract: The invention provides for a fusion protein comprising a 3E10 Fv joined to a Hsp-70, Hsp-27, Hsp-90 or GRP-78or portion thereof, and optionally, the 3E10 Fv comprising an amino acid sequence AGIH at its amino terminus.

Abstract: The invention provides methods for determining whether a subject is suffering from a rheumatoid arthritis associated with the BRAF oncogene comprising contacting isolated fibroblasts from the subject with a molecule or pool of molecules directed to the BRAF oncogene; and culturing the sample in the presence of the agent and determining whether BRAF oncogene expression by the cell is decreased and/or whether cells in the sample return to a less transformed phenotype, exhibit decreased cell proliferation and/or exhibit increased contact inhibition, any of which is indicative that the subject is suffering from a rheumatoid arthritis associated with the BRAF oncogene.

Abstract: The invention provides methods for determining whether a subject is suffering from a rheumatoid arthritis associated with the BRAF oncogene comprising contacting isolated fibroblasts from the subject with a molecule or pool of molecules directed to the BRAF oncogene; and culturing the sample in the presence of the agent and determining whether BRAF oncogene expression by the cell is decreased and/or whether cells in the sample return to a less transformed phenotype, exhibit decreased cell proliferation and/or exhibit increased contact inhibition, any of which is indicative that the subject is suffering from a rheumatoid arthritis associated with the BRAF oncogene.

Abstract: Antibodies that penetrate cell nuclei and inhibit DNA repair or interfere with DNA metabolism are provided for treatment of cancer (both directly and by sensitizing cancer cells to DNA-damaging treatments) or inhibiting or preventing viral infection, proliferation or metabolism. The method involves treating cells with a composition containing cell-penetrating anti-DNA antibodies or derivatives thereof, alone or in combination with treatment that induces DNA damage such as DNA-damaging chemotherapy or radiation. The impact of the cell-penetrating anti-DNA antibodies or derivatives thereof is potentiated in cancer cells that are deficient in DNA repair, and the cell-penetrating anti-DNA antibodies or derivatives thereof are synthetically lethal to cancer cells with DNA repair deficiencies.

Abstract: The invention provides a method for inhibiting an intracellular target in a cell with a bispecific antibody comprising contacting the cell with a bispecific antibody having a first Fv fragment with a cell-penetrating determinant and a second Fv fragment with an intracellular target-binding determinant under suitable conditions so that the first Fv fragment causes the bispecific antibody to enter the cell and the second Fv fragment binds the intracellular target in the cell and thereby inhibiting the intracellular target.

Abstract: The invention provides for a fusion protein comprising a 3E10 Fv joined to a Hsp-70, Hsp-27, Hsp-90 or GRP-78 or portion thereof, and optionally, the 3E10 Fv comprising an amino acid sequence AGIH at its amino terminus.