The present invention provides compositions and methods for treating cancer in a human. The invention includes and relates to administering a genetically modified T cell to express a CAR system wherein the CAR system comprises a polynucleotide encoding multiple signaling-modules with either multiple antibody targeting tumor specific antigen or with membrane bound cytokine to further enhance immune cell survival and proliferation. The multi-costimulatory signaling structure gave less toxicity than conventional CAR-T structures using CD28 signaling domain. A CAR system with multiple antibodies targeting different tumor specific antigen can target difference cancer cell populations simultaneously.
