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In vivo suppression of EL 4 lymphomas by rabbit antitumor sera
Abstract:
Three of more than 50 batches of rabbit antisera raised against the mouse EL 4 lymphoma could inhibit the growth of the tumor in the syngeneic C57BL/6J mice either after exposure of the tumor cells to the antitumor globulin (ATG) in vitro or after the administration of ATG in mice preinoculated with various numbers of EL 4 cells, even though the ATG was not cytotoxic to the tumor cells in the presence of complement. The outcome of immunotherapy with ATG in tumor-bearing C57BL/6J mice depended on the tumor load, the interval between tumor inoculation and the institution of therapy, the total dose, and the schedule of administration of ATG. Complete tumor suppression could be obtained in a proportion of mice preinoculated with 10(5) EL 4 cells, i.e., 10(4) times more than the minimum number of EL 4 cells necessary for 100% tumor takes. Whole-body irradiation (400 rads) or complement depletion of tumor host by cobra venom factor had no effect on tumor suppression by ATG. No evidence of immunity against the EL 4 lymphoma could be detected in EL 4-bearing mice that survived after serotherapy. Anti-EL 4 sera raised in goats and goat and rabbit antisera raised against a lymphoma in the AKR mice have, so far, failed to show any tumor inhibition.
Insights
Antitumor globulin (ATG) effectively inhibited EL 4 lymphoma growth in mice, even without direct cell toxicity. Treatment success depended on factors like tumor burden and ATG dosage, demonstrating potential for cancer immunotherapy.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- Mouse EL 4 lymphoma is a model for studying tumor growth.
- Antisera raised against tumors can potentially be used for immunotherapy.
Purpose of the Study:
- To investigate the efficacy of antitumor globulin (ATG) in inhibiting EL 4 lymphoma growth in vivo.
- To determine factors influencing the success of ATG immunotherapy.
Main Methods:
- Rabbit antisera against EL 4 lymphoma were administered to syngeneic C57BL/6J mice.
- Tumor cells were exposed to ATG in vitro and in vivo.
- Tumor growth inhibition was assessed based on various parameters.
Main Results:
- Three batches of rabbit antisera demonstrated significant inhibition of EL 4 lymphoma growth.
- ATG efficacy was dependent on tumor load, treatment timing, dosage, and schedule.
- Complete tumor suppression was achieved in mice with a high tumor cell inoculation (10^5 cells).
- Whole-body irradiation and complement depletion did not affect ATG's tumor suppression.
- No detectable immunity against EL 4 lymphoma was observed in surviving mice.
Conclusions:
- ATG shows promise as a therapeutic agent against EL 4 lymphoma, independent of complement-mediated cytotoxicity.
- Optimizing treatment parameters is crucial for successful ATG immunotherapy.
- Further research may explore the mechanisms of ATG-mediated tumor suppression.