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L1210/DTIC antigenic subline: studies at the clone level
Abstract:
Treatment of murine tumors with the anti-tumor agent 5-(3,3 dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) has resulted in the induction of antigenic specificities not found in parental cells. After the withdrawal of DTIC treatment, the antigenic sublines maintained the new properties indefinitely, as a heritable character although the mechanism of induction and the molecular nature of the new antigens are essentially unknown. Seven clones from the murine immunogenic leukemia L1210/DTIC were selected and studied in some detail. Three of the seven clones showed an increased immunogenicity in vivo since two clones (D5 and D7) were rejected by syngenic mice and one (D6) prolonged the life span for 3 weeks (untreated tumours killed the mice in 7 days). The seven clones and the L1210/DTIC were recognized and lysed by in vivo primed, in vitro stimulated (with L1210/DTIC) lymphocytes. Therefore, the seven clones shared antigens with the L1210-DTIC immunogenic subline. Secondary stimulated lymphocytes to clone D5, and clone D7 were able to lyse D5, D6 and D7 cells, respectively, but were unable to recognize the remaining clones. From in vivo and in vitro studies, all the L1210/DTIC sublines are composed of cells carrying two or more distinct antigens. Each cell clone expressed one set of antigens. It was concluded that only a few antigens expressed in different cells were induced by a DTIC treatment of L1210 leukemia.
Insights
Treatment with 5-(3,3 dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) induced new, heritable tumor antigens in mice. These novel antigens, expressed by L1210 leukemia sublines, were recognized by the immune system, suggesting potential for targeted cancer therapies.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- The anti-tumor agent 5-(3,3 dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) is used in cancer treatment.
- DTIC treatment induces new antigenic specificities in murine tumor cells.
- These induced antigens are heritable and maintained after DTIC withdrawal.
Purpose of the Study:
- To investigate the immunogenicity and antigenic properties of DTIC-induced murine leukemia L1210 sublines.
- To characterize the antigens expressed by DTIC-treated L1210 leukemia clones.
- To assess the immune system's recognition of these novel tumor-associated antigens.
Main Methods:
- Selection and study of seven clones from L1210/DTIC murine leukemia.
- In vivo assessment of clone immunogenicity using syngenic mice.
- In vitro lymphocyte stimulation and cytotoxicity assays using L1210/DTIC and its clones.
Main Results:
- Three of seven L1210/DTIC clones exhibited increased immunogenicity in vivo.
- DTIC-induced sublines and clones were recognized and lysed by lymphocytes primed with L1210/DTIC.
- Specific lymphocyte responses indicated that each clone expressed distinct sets of antigens, with some shared antigens among sublines.
Conclusions:
- DTIC treatment of L1210 leukemia induces a limited number of distinct antigens expressed across different cell sublines.
- The induced antigenic specificities are heritable and recognized by the host immune system.
- These findings highlight the potential of DTIC-induced antigens in cancer immunotherapy.