Sickle Cell Erythrocytes Kill Solid Tumors Resistant to Chemotherapy and Radiation

Sickle cell erythrocytes bind to and block blood vessels in the hypoxic microenvironment of solid tumors, and the reactive oxygen species (ROS) they release act to destroy the tumor.

Resistance of hypoxic solid tumors to chemotherapy and radiotherapy remains a major challenge to cancer researchers that calls for conceptually new approaches. In a paper published in the January 9, 2013, online edition of the journal PLOS ONE investigators at the Jenomic Research Institute (Carmel, CA, USA) and their collaborators at Duke University (Durham, NC, USA) identified a novel method for killing solid tumors that was based on the tendency of sickle cell erythrocytes to aggregate when exposed to hypoxic conditions.

The investigators found that within minutes after injection sickle cell erythrocytes, but not normal red blood cells, homed and adhered to hypoxic 4T1 tumor vasculature. Hemoglobin saturation levels were at or below 10% and the cells were distributed over 70% of the tumor space. The bound sickle cell erythrocytes formed microaggregates that obstructed or occluded up to 88% of tumor microvessels. When sickle cell erythrocytes, but not normal red blood cells, were combined with the exogenous pro-oxidant zinc protoporphyrin (ZnPP), they induced a potent tumor killing response.

In contrast to existing treatments directed only to the hypoxic tumor cell, the approach described in this paper targeted the hypoxic tumor vascular environment and induced injury to both tumor microvessels and tumor cells using intrinsic sickle cell erythrocyte-derived oxidants and locally generated ROS.

First author Dr. David S. Terman, founder of the Jenomic Research Institute, said, "Sickle cells, unlike normal red blood cells, stick like Velcro to tumor blood vessels where they cluster and shut down the blood supply of oxygen deprived tumors. Once clumped within the tumor, the sickle cells rupture releasing toxic residues that promote tumor cell death. Sickle cell red blood cells appear to be a potent new tool for treatment of hypoxic solid tumors, which are notable for their resistance to existing cancer treatments."

Related Links:
Jenomic Research Institute
Duke University