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Chemotherapy and immunotherapy of L1210 leukemic mice with antigenic tumor sublines
Abstract:
Tumor cells, treated in vivo with anticancer compounds, may acquire new antigenic specificities in addition to any original antigens associated with parental tumors. Treatment of mice carrying the parental leukemias L1210 Ha or L1210 Cr with leukemia cells antigenically altered by treatment with 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (L1210 Ha/DTIC and L1210 Cr/DTIC, respectively) was essentially ineffective in prolonging the life span of the animals. However, synergic therapeutic activity was exhibited by administration of L1210 Ha/DTIC cells plus 1,3-bis(2-chloroethyl)-1-nitrosourea in the treatment of the moderately immunogenic L1210 Ha leukemia and by the combination of L1210 Cr/DTIC cells and lymphocytes immune to L1210 Cr/DTIC administered with 1,3-lymphocytes immune to L1210 Cr/DTIC administered with 1,3-bis(2-chloroethyl)-1-nitrosourea in the treatment of the low immunogenic L1210 Cr leukemia. Early and advanced L1210 Cr-bearing mice showed marked increases in survival time and a significant number of tumor-free survivors on treatment with cyclophosphamide followed by transfer of lymphocytes immune to L1210 Cr/DTIC cells. When parental tumor cells were used as the immunogen, the therapeutic effect was diminished. Thus, in the current investigation, although immunotherapy per se was essentially ineffective, the immunochemotherapeutic modalities used were successful in markedly increasing the survival time of leukemic animals and resulted in an incidence of cures.
Insights
Anticancer drug treatment can alter tumor antigens. Combining chemotherapy with altered leukemia cells or immune cells significantly improved survival and cure rates in mice with leukemia.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Anticancer drug treatment can induce new antigenic specificities in tumor cells.
- Parental leukemia cells treated with 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) showed limited therapeutic effect alone.
- Tumor immunogenicity influences treatment response.
Purpose of the Study:
- To evaluate the efficacy of immunochemotherapeutic strategies in leukemia treatment.
- To investigate the synergistic effects of combining altered tumor cells and chemotherapy.
- To assess the impact of immune cell transfer combined with chemotherapy.
Main Methods:
- Treatment of mice with L1210 Ha/DTIC and L1210 Cr/DTIC cells, alone and in combination with 1,3-bis(2-chloroethyl)-1-nitrosourea.
- Administration of L1210 Cr/DTIC cells combined with immune lymphocytes and chemotherapy.
- Treatment with cyclophosphamide followed by transfer of lymphocytes immune to L1210 Cr/DTIC cells.
Main Results:
- Combined therapy of L1210 Ha/DTIC cells and chemotherapy showed synergistic activity against L1210 Ha leukemia.
- Combination of L1210 Cr/DTIC cells, immune lymphocytes, and chemotherapy was effective against L1210 Cr leukemia.
- Cyclophosphamide followed by immune lymphocyte transfer significantly increased survival and cure rates in L1210 Cr leukemia models.
Conclusions:
- Immunochemotherapeutic approaches, combining altered tumor cells or immune cells with chemotherapy, are effective in leukemia treatment.
- Synergistic therapeutic activity was observed, leading to increased survival times and tumor cures.
- The use of antigenically altered tumor cells and immune cells enhances therapeutic outcomes in leukemia.