Abstract: Provided herein are compositions and methods for promoting hematopoietic cell cytotoxicity.

Abstract: This disclosure relates to engineered cells, such as T-cells, comprising targeted chimeric antigen receptors. In certain embodiments, T-cell targeted chimeric antigen receptors (CAR) are expressed at higher levels when endogenous expression of a T-cell antigen is knocked-down or reduced in the T-cells. In certain embodiments, the engineered cells are immunoregulatory cells genetically modified to prevent or reduce T-cell antigen expression, or the immunoregulatory cells contain a nucleic acid that reduces or knocksdown T-cell mRNA expression, under conditions such that reduced expression of the T-cell antigen results in an increased expression of a chimeric antigen receptor compared to similarly situated immunoregulatory cells wherein the expression of the T-cell antigen is not altered or reduced. In certain embodiments, T-cell antigens include, but are not limited to, CD5, CD7 and CD3.