Interferons alpha and gamma differ in their ability to cause tumour stasis and regression in vivo

We have studied the antitumour activity of human lymphoblastoid interferon-alpha [HuIFN-alpha(N)] and human recombinant interferon-gamma (rHuIFN-gamma) on 12 early passage (passages 2-7) human tumour xenografts derived from primary malignancies. Systemic daily therapy of established (approx. 0.5 cm diameter) subcutaneous xenografts with HuIFN-alpha(N) resulted in significant tumour stasis, and occasionally regression, in nine of 12 breast, bowel, and ovarian cancers studied. A significant decrease in tumour mitotic index was seen in three HuIFN-alpha(N) sensitive breast tumours. In contrast, none of nine of the same tumours responded significantly to rHuIFN-gamma therapy. Direct administration of rHuIFN-gamma into the tumour did not improve its therapeutic efficacy. However, when tumour cells from xenografts were dissociated and grown as colonies in soft agar, both IFNs, used at doses that are found circulating in vivo after therapy, inhibited colony development in three of three lines tested. Combinations of rHuIFN-gamma and HuIFN-alpha(N) had no synergistic benefit in four of four xenografts studied.