Chimeric antigen receptors (CARs) can provide anti-tumor specificity, and adoptive transfer of CAR-modified stem cells offers a method to introduce and expand tumor specific T-cells. This adoptive immunotherapy can eliminate malignant cells or supplement traditional therapies. The use of a single chain TCR (scTCR) in which the TCR Vα and Vβ segments are joined by a flexible linker provides a better alternative to introduction of full length TCR genes. We have developed a HER2 specific scTCR as well as a single chain antibody based receptor (scFv) to increase avidity to the tumor antigen and avoid the potential limitation of MHC restriction. Our lab has previously developed a signaling cassette based on the CD28 and p56Lck proteins which are prominent in the T-cell signaling pathway. The single chain specificities are linked to the signaling cassette that we have shown to function in T-cells. With specificity and signaling coupled, the chimeric antigen receptor can be transduced into hematopoietic stem cells (HSC). Engraftment of the transduced HSC shows multiple cell types expressing our transgene reporter. Anti-tumor activity of transduced cells is measured by cytokine release upon stimulation.