The present disclosure provides ex vivo methods which employ modified cells of leukemic origin to enhance the efficacy of adoptive cell therapy.

The present disclosure relates to inhibitors of DNA protein kinase, and compositions and methods of use thereof. In some embodiments, the inhibitors have the structure of Formula I:

##STR00001## or a salt thereof, wherein: x.sub.1 is CR.sub.3 or N; R.sub.1 is C.sub.1-C.sub.3 alkyl; R.sub.2 is cycloalkyl or heterocyclyl, and cycloalkyl and heterocyclyl are optionally substituted with one or more R.sub.6; R.sub.3 is H or C.sub.1-C.sub.3 alkyl; R.sub.4 is H or C.sub.1-C.sub.3 alkyl; R.sub.5 is C.sub.1-C.sub.3 alkyl; each R.sub.6 is independently selected from hydroxy, halo, alkyl, alkoxy, cycloalkyl, amino, and cyano, or two R.sub.6, taken together with the atom or atoms to which they are bonded, form a spirocyclic or fused ring; and R.sub.7 is H or C.sub.1-C.sub.3 alkyl.

The invention is in the field of medical sciences. It provides means and methods for the treatment of cancer. More in particular, it provides cells and cell lines that can be developed into fully functional dendritic cells. These cells endogenously express cancer-specific antigens, which makes them particularly suited for the treatment of different kinds of cancer. More in particular, the invention relates to a precursor cell line for dendritic cells called DC-One as deposited at the DSMZ under accession number DSMZ ACC3189 on Nov. 15, 2012.

Provided is a method for isolating and proliferating autologous cancer antigen-specific CD8.sup.+ T cells, and more particularly, a method for selecting an epitope recognized by CD8.sup.+ T cells from autologous cancer antigens present in blood of individual cancer patients; and isolating autologous cancer antigen-specific CD8.sup.+ T cells by using a peptide of the selected epitope, and a method of massively proliferating CD8.sup.+ T cells by using the method. According to the present invention, it is possible to isolate autologous cancer antigen-specific CD8.sup.+ T cells by using the peptide of the CD8 T cell epitope of the autologous cancer antigen present in blood of individual cancer patients instead of a heterologous antigen. Therefore, by using T cells recognizing the autologous cancer antigen, it is possible to effectively select and eliminate cancer cells derived from the cancer patient's own cells. Thus, T cells can be applied to treatment and alleviation of cancer diseases without side effects.

Disclosed herein are methods and compositions for modifying TCR genes, using nucleases (zinc finger nucleases or TAL nucleases) to modify TCR genes.

The present disclosure relates to mRNA, self-replicating RNA, and temperature-sensitive, self-replicating RNA encoding a cancer antigen. The RNA constructs are suitable for cancer immunotherapy in a mammalian subject, such as a human subject.

Disclosed are compositions and methods for treatment of breast cancer. Disclosed methods and compositions include dendritic cells loaded with cyclin B1 and WT-1 peptide antigens for immunotherapy. These dendritic cell vaccines are administered alone or in combination with other cancer therapies to improve outcomes. Disclosed methods also involve the use of therapeutic agents, such as anakinra, that block the IL-1 inflammation pathway. These agents are used in combination with chemotherapy and/or immunotherapy in treating breast cancer.

Disclosed are compositions and methods for treatment of breast cancer. Disclosed methods and compositions include dendritic cells loaded with cyclin B1 and WT-1 peptide antigens for immunotherapy. These dendritic cell vaccines are administered alone or in combination with other cancer therapies to improve outcomes. Disclosed methods also involve the use of therapeutic agents, such as anakinra, that block the IL-1 inflammation pathway. These agents are used in combination with chemotherapy and/or immunotherapy in treating breast cancer.

A cell for immunotherapy of the present invention includes a nucleic acid encoding a Wilms tumor 1 gene product or a fragment of the Wilms tumor 1 gene product, wherein the nucleic acid including (i) a region encoding a fragment of the Wilms tumor 1 gene product, the fragment being indicated by positions 194 to 493 of amino acid sequence of SEQ ID NO:1 or by positions corresponding to the positions 194 to 493 of amino acid sequence corresponding to SEQ ID NO:1 and (ii) only one AUG as a functional start codon, connected to a 5 terminal side of the region via 3m (m is 124-192) bases intervening between the AUG as the functional start codon and the 5 terminal side of the region, and a nucleic acid encoding CD1d, wherein the cell has been loaded with a glycolipid recognized by antigen receptor of NKT cell.

Disclosed herein are methods and compositions for modifying TCR genes, using nucleases (zinc finger nucleases or TAL nucleases) to modify TCR genes.