Adoptive immunotherapy using ex vivo cultured tumour-infiltrating lymphocytes (TIL) has shown great promise as a form of cancer therapy for relatively immunogenic cancers such as melanoma. However, it is difficult to isolate TILs specific for a tumour antigen in the majority of malignancies. An alternate source of tumour-specific lymphocytes can be derived by genetic modification of autologous T lymphocytes with chimeric antigen receptors (CAR), conferring antigen specificity in a major histocompatability complex (MHC) independent manner. While CAR-expressing CD8+ T lymphocytes have shown to be effective in adoptive immunotherapy, recent evidence has suggested that a concerted effort between multiple immune subsets may enhance the anti-tumour response. However, due to current limitations in genetic modification, the ability of many leukocytes to perform anti-tumour effector functions when expressing a CAR has yet to be explored. To address this issue, we generated a novel mouse model in which the expression of a CAR specific for the Her2 antigen was driven by the pan-hematopoietic promoter, vav. In our Vav-CAR mouse model, we demonstrate that multiple immune subsets are capable of expressing a functional CAR, and mediate antigen specific responses through cytokine release and cytotoxicity. Adoptive transfer of activated CAR T cells into tumour-bearing wild-type mice mediated significant inhibition of established tumours. Furthermore, upon tumour challenge, naïve Vav-CAR mice are able to mount an effective anti-tumour response upon recognition of the Her2 antigen, without any prior immunisation or activation, and this tumour rejection was dependent on the presence of both Natural Killer cells and CD8+ T cells. In ongoing studies, we plan to elucidate the ability of other leukocytes to mediate anti-tumour activity when expressing a CAR, and to elucidate the optimal combination of CAR expressing leukocytes for adoptive immunotherapy.