Abstract
A MAb (B16G) which recognizes a constant epitope on TsC and their soluble factors in DBA/2 mice has been described previously. In this study, we show that when this MAb is covalently linked to the photoactivable molecule Hp, and injected i.v. into P815 tumor-bearing mice which were subsequently exposed to light, tumors undergo permanent regression in 10%–40% of these mice (depending on the individual experiment). All control animals died within an average of 22–24 days after tumor cell injection. It is suggested that tumor regression is attributable to immune mechanisms facilitated by the elimination of a population of TsC. When splenocytes of B16G-Hptreated mice were assayed in vitro for the generation of CTL active against P815 tumor cells, it was found that 24 h after treatment, a significant increase in killer cell activity was noted but that this effect was gone by 48h. We also show that B16G-Hp conjugates are capable in vitro of specifically killing cells of a TsC hybridoma, A10 (which has been shown previously to secrete a T suppressor factor reactive with P815 cell surface antigens). This conjugate had no cytotoxic effect on P815 cells under conditions in which A10 cells were killed.
Keywords: Soluble Factor, Suppressor Cell, P815 Cell, P815 Tumor, Cell Injection
Abbreviations
- CTL
cytotoxic T lymphocytes
- C-MAb
control monoclonal antibody
- EDCI
1-ethyl-3-(3-diemthylaminopropyl) carbodiimide
- Hp
hematoporphyrin
- MAb
monoclonal antibody
- PBS
phosphate-buffered saline
- RαMIg
rabbit antimouse Ig
- TsC
T suppressor cell
- TsF
T suppressor factor
- FCS
fetal calf serum
- DME
Dulbecco's modified Eagle's medium
References
- 1.Bertschmann M, Lüscher EF. Stimulation of different pathways of T cell functions by syngeneic tumor cells and soluble membrane proteins. Cell Immunol. 1983;78:13. doi: 10.1016/0008-8749(83)90255-1. [DOI] [PubMed] [Google Scholar]
- 2.Dougherty TJ, Kaufman JH, Goldfarb A, Weishaupt KR, Boyle D, Mittleman A. Photoradiation therapy for the treatment of malignant tumors. Cancer Res. 1978;38:2628. [PubMed] [Google Scholar]
- 3.Dougherty TJ, Lawrence G, Kaufman JH, Boyle D, Weishaupt KR, Goldfarb A. Photoradiation in the treatment of recurrent breast cancer. J Natl Cancer Inst. 1979;62:231. [PubMed] [Google Scholar]
- 4.Maier T, Stammers AT, Levy JG. Characterization of a monoclonal antibody directed to a T cell suppressor factor. J Immunol. 1983;131:1843. [PubMed] [Google Scholar]
- 5.Mew D, Wat C-K, Towers GHN, Levy JG. Photoimmunotherapy: treatment of animal tumors with tumor-specific monoclonal antibody-hematoporphyrin conjugates. J Immunol. 1983;130:1473. [PubMed] [Google Scholar]
- 6.Mew D, Lum V, Wat C-K, Towers GHN, Sun C-HC, Walter RJ, Wright W, Berns MW, Levy JG. Ability of specific monoclonal antibodies and conventional antisera conjugated to hematoporphyrin to label and kill selected cell lines subsequent to light activation. Cancer Res. 1985;45:4380. [PubMed] [Google Scholar]
- 7.Nagarkatti M, Kaplan AM. The role of suppressor T cells in BCNU-mediated rejection of syngeneic tumor. J Immunol. 1985;135:1510. [PubMed] [Google Scholar]
- 8.Steele JK, Stammers AT, Levy JG. Preliminary characterization of a soluble immunosuppressive molecule from DBA/2 spleen cells using monoclonal antibody immunoadsorbence. Cell Immunol. 1984;90:303. doi: 10.1016/0008-8749(85)90195-9. [DOI] [PubMed] [Google Scholar]
- 9.Steele JK, Stammers AT, Levy JG. Isolation and characterization of a tumor specific T suppressor factor from a T cell hybridoma. J Immunol. 1985;135:1201. [PubMed] [Google Scholar]
- 10.Steele JK, Stammers AT, Levy JG. Preliminary characterization of human T cell suppressor factor (HTsF) isolated from tonsil cells by monoclonal antibody immunoadsorbence. J Immunol. 1985;135:1201. [PubMed] [Google Scholar]
- 11.Steele JK, Singhai R, Tench Stammers A, Levy JG. Immunization of DBA/2 mice with a T cell hybridoma-derived TsF increases immune resistance to the syngeneic tumors P815 and L1210. J Immunol. 1986;177:3025. [PubMed] [Google Scholar]
- 12.Steele JK, Chan A, Stammers AT, Singhai R, Levy JG (1987) Immune regulation in neoplasia: dominance of suppressor systems. In: Induction and recognition of the transformed cell. Plenum, (in press)
- 13.Takei F, Levy JG, Kilburn DG. In vitro induction of cytotoxicity against syngeneic mastocytoma and its suppression by spleen and thymus cells from tumor bearing mice. J Immunol. 1976;116:288. [PubMed] [Google Scholar]
- 14.Takei F, Levy JG, Kilburn DG. Characterization of suppressor cells in mice bearing syngeneic mastocytoma. J Immunol. 1977;118:412. [PubMed] [Google Scholar]
- 15.Takei F, Levy JG, Kilburn DG. Characterization of a soluble factor which specifically suppresses the in vitro generation of cells cytotoxic for syngeneic tumor cells in mice. J Immunol. 1978;120:1218. [PubMed] [Google Scholar]
