Resistance of randomly dispersed and oxygen-starved lung tumor cells to chemo- and radiotherapy constitutes the vast majority recurrences and death from lung cancer. We use sickle cells derived from humans with sickle cell anemia to target oxygen-deprived tumor cells that persist and multiply after conventional treatment. Transfused sickle cells selectively occluded tumor microvessels and shut down blood flow to these oxygen-deprived pockets leading to tumor cell death and complete shrinkage of aggressive lung tumors. Combining the sickle cells with a vascular disrupting agents and radiation injure and narrow tumor blood vessels, amplified the scale of sickle cell-induced blood vessel closure and tumor cell killing. The strength of the tumor killing produced by this combination exceeded that of either agent alone or combined with conventional anti-angiogenics, chemotherapy or radiation. Combinatorial sickle cells-Combretastatin treatment thereby constitutes a major advance toward eradicating treatment-resistant tumor cells and reducing the frequency of lung cancer recurrence.
