Table 2.
Long-lived amplification of tumor-protective immunity by a tumor-specific antibody IL-2 fusion protein
| VaccinationChallenge ↓↓ | Determination of metastases ↓ | |||
|---|---|---|---|---|
| Day 0 | 90↑↑↑↑↑100 Treatment | 110 | 120 | |
|
| ||||
| Vaccine | Treatment | Bone marrow metastasis | Liver metastasis | Liver weight, mg |
| scIL-12 NXS2 | PBS | 2,2,2,2,2,1 | 4,4,4,2,2,1 | 2,451 ± 723 |
| scIL-12 NXS2 | ch14.18 + IL-2 | 2,2,2,1,1,1 | 3,3,2,2,2,1 | 2,192 ± 823 |
| scIL-12 NXS2 | ch225-IL-2 | 2,2,2,1,1,0 | 4,3,3,1,1,1 | 1,810 ± 650 |
| scIL-12 NXS2 | ch14.18-IL-2* | 0,0,0,0,0,1 | 0,0,0,0,0,0 | 981 ± 88 |
Mice were vaccinated by s.c. injection of 5 × 106 NXS2 cells genetically engineered to produce scIL-12 and challenged by a lethal i.v. injection of 5 × 104 NXS2 wild-type cells 90 days after initial vaccination. Treatment was initiated at day 5 after tumor cell challenge by five daily i.v. injections of PBS; 10 μg of ch14.18 antibody + 30,000 units of rhIL-2, 10 μg of the nonspecific ch225-IL-2 fusion protein, or 10 μg of the tumor-specific ch14.18-IL-2 fusion protein. Bone marrow metastases were staged according to results obtained by high- and low-sensitivity tyrosine hydroxylase RT-PCR. Liver metastases were staged according to the percentage of metastatic liver surface as follows: 0, 0%; 1, <0–25%; 2, 25–50%; 3, 50–75%; 4, >75%. Data for liver weight are the mean ± SD.
Differences in bone marrow staging, liver metastasis, and liver weights between fusion-protein-treated mice and all control groups were statistically significant (P < 0.01).