The invention relates to compositions and methods of SIRP-α variant constructs including SIRP-α variants. The SIRP-α variant constructs may be engineered in a variety of ways to respond to environmental factors, such as pH, hypoxia, and/or the presence of tumor-associated enzymes or tumor-associated antigens. The SIRP-α variant constructs of the invention may be used to treat various diseases, such as cancer, preferably solid tumor or hematological cancer.
