Detection of Early and Delayed Antitumor Effects following Curative Adoptive Chemoimmunotherapy of Established Leukemia1
نویسندگان
چکیده
Advanced disseminated leukemia can be successfully erad icated by treatment with a combination of noncurative nonlethal chemotherapy plus adoptively transferred immune cells. The time course of tumor elimination following such therapy was examined by bioassay for tumor of peripheral blood and spleen cells from treated mice. Curative treatment with adoptive chemoimmunotherapy did not immediately eliminate all leukemia. Bioassay of cells from treated mice, rather, demonstrated that, following the initial tumor lysis mediated by the chemotherapy and immune cells, a period of tumor regrowth lasting several weeks preceded ultimate tumor eradication. This transient tu mor regrowth detectable by bioassay never became clinically evident in the treated mice. However, immunosuppression of mice two weeks after treatment with adoptive chemoimmunotherapy resulted in recurrence of lethal tumor. The results suggest that tumor elimination following curative adoptive chemoimmunotherapy is biphasic and that the efficacy of therapy may be subject to positive and/or negative influences over a prolonged time period.
منابع مشابه
Detection of early and delayed antitumor effects following curative adoptive chemoimmunotherapy of established leukemia.
Advanced disseminated leukemia can be successfully eradicated by treatment with a combination of noncurative nonlethal chemotherapy plus adoptively transferred immune cells. The time course of tumor elimination following such therapy was examined by bioassay for tumor of peripheral blood and spleen cells from treated mice. Curative treatment with adoptive chemoimmunotherapy did not immediately ...
متن کاملImmunotherapeutic strategies including transplantation: eradication of disease.
Although there have been recent advances with targeted therapies in chronic lymphocytic leukemia (CLL), chemoimmunotherapy remains the treatment of choice; however, this approach is not curative. A key feature of CLL is that it induces a state of immunosuppression, causing increased susceptibility to infections and failure of an antitumor immune response, often worsened by the immunosuppressive...
متن کاملUnleashing the power of anti-tumor CD4+ T cells: novel insights into the curative mechanisms of chemoimmunotherapy for cancer
Background CD4 T cells are critical mediators of anti-tumor immunity and orchestrate a broad range of immune responses against cancer. Previous studies from our lab and others have demonstrated that, adoptive transfer of tumor specific CD4 T cells to lymphopenic hosts led to eradication of established tumors in mice models. Accumulating evidence from preclinical and clinical studies also sugges...
متن کاملUnraveling cancer chemoimmunotherapy mechanisms by gene and protein expression profiling of responses to cyclophosphamide.
Certain chemotherapeutic drugs, such as cyclophosphamide (CTX), can enhance the antitumor efficacy of immunotherapy because of their capacity to modulate innate and adaptive immunity. Indeed, it has been argued that this capacity may be more significant to chemotherapeutic efficacy in general than is currently appreciated. To gain insights into the core mechanisms of chemoimmunotherapy, we meth...
متن کاملMicroenvironment and Immunology Unraveling Cancer Chemoimmunotherapy Mechanisms by Gene and Protein Expression Profiling of Responses to Cyclophosphamide
Certain chemotherapeutic drugs, such as cyclophosphamide (CTX), can enhance the antitumor efficacy of immunotherapy because of their capacity to modulate innate and adaptive immunity. Indeed, it has been argued that this capacity may be more significant to chemotherapeutic efficacy in general than is currently appreciated. To gain insights into the core mechanisms of chemoimmunotherapy, we meth...
متن کامل