Recombinant Human Tumor Necrosis Factor Enhances Radiosensitivity and Improves Animal Survival in Murine Neuroblastoma

Abstract

An analysis of the potential of recombinant human tumor necrosis factor to enhance the radiosensitivity of C1300 murine neuroblastoma was undertaken. Female A/J mice bearing C1300 murine neuroblastoma (right hindlimb) underwent the following treatments: group 1—0.25 cc normal saline intraperitoneally times 2, group 2—0.5 mcg./gm. recombinant human tumor necrosis factor intraperitoneally times 2, group 3—400 cGy. right hindlimb, group 4—800 cGy. right hindlimb, group 5—400 cGy. right hindlimb plus 0.5 mcg./gm. recombinant human tumor necrosis factor intraperitoneally times 2 and group 6—800 cGy. right hindlimb plus 0.5 mcg./gm. recombinant human tumor necrosis factor intraperitoneally times 2. All animals were followed for 21 days after treatment initiation with interval measurements of tumor volume. All single modality treatments were more effective than normal saline in reducing average tumor volumes during the study period (800 cGy. equals recombinant human tumor necrosis factor greater than 400 cGy. greater than normal saline). The addition of recombinant human tumor necrosis factor to radiotherapy moderately augmented antitumor response at radiation doses of 400 cGy. but marked enhancement was attained at radiation doses of 800 cGy. (p <0.02). This enhancement was achieved without increased animal morbidity or mortality. Animals receiving recombinant human tumor necrosis factor in addition to 800 cGy. demonstrated increased survival when compared with animals receiving 800 cGy. alone (p <0.02). Although statistical synergy was not proved, recombinant human tumor necrosis factor appears to augment significantly radiation-induced tumor regression at no toxic cost to the animal.