Factors affecting passive monoclonal antibody therapy of Moloney sarcoma in BALB/c mice.
We have developed a syngeneic monoclonal antibody (MoAb) (244-19A) which retards growth and contributes to cures of BALB/c mice bearing Moloney sarcoma cell (MSC) tumors (S.J. Kennel, T. Lankford, and K.M. Flynn, Cancer Res., 43: 2843-2847, 1983). The 244-19A epitope has not been detected in normal tissue or in any cultured cell (other than MSC) tested, including 15 different BALB/c sarcomas. MoAb 244-19A remains in circulation for a relatively long time in normal mice (t1/2 = 3.8 days), but it is cleared faster from tumor-bearing mice (t1/2 = 1.7 days), indicating a specific interaction of the antibody with the tumor. The 244-19A epitope is very labile. Osmotic lysis of cells or fixation with ethanol abolishes antibody binding. Trypsin treatment or fixation with gluteraldehyde reduces activity by 80 to 90%. Results from immunoprecipitation of radioiodinated MSC surface proteins indicate that the 244-19A epitope may reside on a Mr 65,000 protein, distinct from the major C-type virus glycoprotein 70 of these cells. Several factors affecting passive MoAb therapy have been evaluated. Doses as low as 24 micrograms/ mouse demonstrated a significant therapeutic effect; however, larger doses up to 1.5 mg/mouse produced progressively more cures. Since MoAb 244-19A is syngeneic in BALB/c mice, fractionated doses of antibody can be given over long periods of time without a host response to the MoAb. Fractionated doses showed a slight advantage over single dose therapy, but the difference was not statistically significant (P less than 0.2). Passive MoAb therapy has been effective in nu/nu mice, in BALB/c mice depleted of complement with cobra venum factor, and in BALB/c mice irradiated with 399 rads of X-rays; thus, therapy did not require complement, B-cells, or a cytotoxic T- cell response. Although tumor growth was retarded in nu/nu mice (T-cell-deficient), complete cures of tumored animals could not be accomplished even with large, multiple doses of antibody, indicating that cytotoxic T-cells eliminate residual tumor cells resulting in cures of BALB/c mice. Treatment of BALB/c mice with silica to deplete macrophage function did not affect therapy with MoAb 244-19A; however, treated animals still retained about 30% of their original phagocytic function, so macrophages cannot be eliminated as a possible host effector function.
S J
SJ
Kennel
P K
PK
Lankford
K M
KM
Flynn
R
R
Winegar
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity; D000951:Antigens, Neoplasm / Q000032:analysis; D003165:Complement System Proteins / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D000939:Epitopes / Q000032:analysis; D007116:Immunization, Passive; D007457:Iodine Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C; D008980:Moloney murine sarcoma virus; D010587:Phagocytosis / Q000528:radiation effects; D012513:Sarcoma, Experimental / Q000276:immunology / Q000628:therapy*
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000939:Epitopes; D007457:Iodine Radioisotopes; D003165:Complement System Proteins