Abstract: Systems and methods are presented that allow for selection of tumor neoepitopes that are then used to generate a recombinant polytope that is optimized for proper trafficking and processing. In preferred methods, the polytope is encoded in a viral expression system that is used as a therapeutic agent.

Abstract: Cancer is treated using coordinated treatment regimens that uses various compounds and compositions that drive a tumor from the escape phase of cancer immunoediting to the elimination and equilibrium phase of cancer immunoediting.

Abstract: NK cell based cancer immunotherapy, and particularly genetically modified NK92 cell-based immunotherapy is enhanced by expression CXCL12 and/or by suppression or deletion of CXCR4 in the natural killer cells to so reduce aggregation, rejection, and/or fratricide of the natural killer cells. Provided herein are genetically engineered NK (natural killer) cell comprising a recombinant nucleic acid encoding at least a portion of chemokine C—X—C motif ligand 12 (CXCL12), and a transcript for downregulation of chemokine C—X—C motif receptor 4 (CXCR4).