ABSTRACT
Chimeric antigen receptor T (CAR-T) cell therapy is a breakthrough in cancer treatment. With the widespread use of this therapy, increasing evidence is available that CAR-T cell therapy is associated with acute kidney injury (AKI). Nephrologists need to understand the potential nephrotoxicity arising from CAR-T cell therapy. Determining the cause of AKI is a key factor of clinical management. This review focuses on the clinical use of CAR-T cell therapy and the cause and outcomes of nephrotoxicity with its use. We also provide clinical suggestions for clinicians towards both better diagnosis and management of AKI in those receiving CAR-T cell therapy.
Subject(s)
Acute Kidney Injury/diagnosis , Acute Kidney Injury/therapy , Immunotherapy, Adoptive/adverse effects , Receptors, Chimeric Antigen/metabolism , T-Lymphocytes/transplantation , Acute Kidney Injury/immunology , Animals , Cytokine Release Syndrome/diagnosis , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/therapy , Early Diagnosis , Humans , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/immunology , Lymphohistiocytosis, Hemophagocytic/therapy , Prognosis , Receptors, Chimeric Antigen/genetics , Receptors, Chimeric Antigen/immunology , Risk Assessment , Risk Factors , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Tumor Lysis Syndrome/diagnosis , Tumor Lysis Syndrome/immunology , Tumor Lysis Syndrome/therapyABSTRACT
Cell death cannot go unnoticed. It demands that the surrounding cells clear away the corpses in a manner appropriate to the type of cell death. Dying cells represent a threat to the body that should be eliminated by the host immune response. Inflammasome activation followed by IL-1alpha release and IL-1beta maturation is crucial for tackling pathological conditions, including infections, whereas inflammasome activation precedes inflammatory pyroptotic cell death. On the other hand, recent studies have shown that the inflammasome plays an important role in the pathogenesis of metabolic diseases, including obesity, diabetes, and atherosclerosis. Here, we review current knowledge of the association between cell death, excess metabolites, and inflammasome activation as it relates to chronic inflammatory diseases.
Subject(s)
Inflammasomes/immunology , Animals , Atherosclerosis/immunology , Cell Death , Cholesterol, LDL/immunology , Gout/immunology , Humans , Tumor Lysis Syndrome/immunologyABSTRACT
This unit describes two different protocols for the measurement of tumor cytolysis by macrophages. Traditionally, cytotoxicity assays have relied on the use of radioactive isotopes. In Basic Protocol 1, cytotoxic activity is measured by the release into the culture supernatant of a radioisotope that had been incorporated by the target cell and is released upon cell death. This poses a problem for some cell lines in which spontaneous isotope release occurs in the absence of effector cell cytotoxicity. In Basic Protocol 2, a nonradioactive approach is used to measure cytolysis that relies on the fluorescence staining of tumor cells with cell-death markers. It also provides the obvious advantage of avoiding the use of hazardous radioactive materials.
Subject(s)
Cytotoxicity, Immunologic , Macrophages/immunology , Radionuclide Imaging/methods , Tumor Lysis Syndrome/diagnosis , Tumor Lysis Syndrome/immunology , Animals , Cell Line, Tumor , Coculture Techniques , Humans , MiceABSTRACT
An increasing body of literature has documented the usefulness of donor lymphocyte infusions in inducing remissions in patients relapsing post allogeneic hematopoietic progenitor cell transplantation. Efficacy was shown to depend on the disease entity; the best results have been reported in chronic myeloid leukemia in chronic phase, where the remission rate varied between 60 and 80%. In acute myeloid leukemia and myelodysplastic syndromes the remission rate ranged between 20 and 40% and in multiple myeloma the response rate was approximately 40%. In contrast, results have been poor in acute lymphoid leukemia with only 10-20% and even lower reported responses. Considering the efficacy of donor lymphocyte infusions in inducing responses in several hematologic neoplasias post allogeneic transplantation, as will be described in detail in this review, it is justified to anticipate an increasing role for this modality of treatment in relapsed non transplanted patients and as maintenance of the responses achieved with chemotherapy at conventional or high doses.
Subject(s)
Hematologic Neoplasms/etiology , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation , Immunotherapy, Adoptive/methods , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Lymphocyte Transfusion/methods , Humans , Killer Cells, Natural/immunology , Multiple Myeloma/therapy , Recurrence , T-Lymphocytes/immunology , Tumor Lysis Syndrome/immunologyABSTRACT
Un número creciente de publicaciones ha demostrado claramente que la infusión de infusión de linfocitos provenientes del dador original es capaz de reinducir remisiones en pacientes con recaídas luego de un trasplante alogénico de células precursoras hematopoyéticas. También se ha comunicado que la efectividad de la misma varía en las distintas patologías en la que se ha utilizado. Los mejores resultados se obtuvieron en leucemia mieloide crónica, con un rango de remisiones entre 60 y 80 por ciento, mientras que los pacientes con leucemia aguda mieloblástica o síndromes melodisplásicos mostraron porcentajes de remisiones del orden del 20 a 40 por ciento y y pacientes con mieloma múltiple un nível de respuestas próximo a 40 por ciento. En cambio en leucemia aguda linfoblástica los resultados han sido por lo general desalentadores, con un rango de respuestas de apenas 10-20 por ciento y aun inferiores en algunas series. Dada la eficacia de las ILD en ciertas recaidas hematológicas post trasplante alogénico como se expondrá en detalle en esta revisión, es justificado anticipar la extensión de su indicación a pacientes recaídos no trasplantados y como terapia de mantenimiento de la remision obtenida por quimioterapia convencional o a altas dosis.
Subject(s)
Humans , Hematologic Neoplasms/etiology , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Lymphocyte Transfusion/methods , Killer Cells, Natural/immunology , Multiple Myeloma/therapy , Recurrence , T-Lymphocytes/immunology , Tumor Lysis Syndrome/immunologyABSTRACT
Un número creciente de publicaciones ha demostrado claramente que la infusión de infusión de linfocitos provenientes del dador original es capaz de reinducir remisiones en pacientes con recaídas luego de un trasplante alogénico de células precursoras hematopoyéticas. También se ha comunicado que la efectividad de la misma varía en las distintas patologías en la que se ha utilizado. Los mejores resultados se obtuvieron en leucemia mieloide crónica, con un rango de remisiones entre 60 y 80 por ciento, mientras que los pacientes con leucemia aguda mieloblástica o síndromes melodisplásicos mostraron porcentajes de remisiones del orden del 20 a 40 por ciento y y pacientes con mieloma múltiple un nível de respuestas próximo a 40 por ciento. En cambio en leucemia aguda linfoblástica los resultados han sido por lo general desalentadores, con un rango de respuestas de apenas 10-20 por ciento y aun inferiores en algunas series. Dada la eficacia de las ILD en ciertas recaidas hematológicas post trasplante alogénico como se expondrá en detalle en esta revisión, es justificado anticipar la extensión de su indicación a pacientes recaídos no trasplantados y como terapia de mantenimiento de la remision obtenida por quimioterapia convencional o a altas dosis. (AU)
Subject(s)
Humans , Lymphocyte Transfusion/methods , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Hematologic Neoplasms/etiology , Hematologic Neoplasms/therapy , Killer Cells, Natural/immunology , Tumor Lysis Syndrome/immunology , Recurrence , T-Lymphocytes/immunology , Multiple Myeloma/therapyABSTRACT
BACKGROUND: Herpes simplex virus (HSV)-1716, a replication-restricted herpes simplex virus type 1, has shown efficacy as an oncolytic treatment for central nervous system tumors, breast cancer, ovarian cancer, and malignant mesothelioma. We evaluated the efficacy of HSV-1716 in a murine lung cancer model, Lewis lung carcinoma. METHODS: Lewis lung carcinoma cells were infected with HSV-1716 and implanted in the flanks of mice at varying ratios of infected to uninfected cells. Tumor burden was assessed by measurement of the weight of the tumor nodule. The role of the immune system was examined by performing experiments in both immunocompetent and SCID mice. Tumors were implanted in the opposite flank to evaluate the vaccine effect. RESULTS: In immunocompetent and SCID animals, ratio of 1:10 (infected-to-uninfected) cells completely prevented tumor formation and ratio of 1:100 suppressed tumor growth. Established tumors at a distant site in the groups receiving HSV-1716 infected cells showed no difference in size versus control, suggesting absence of a vaccine effect. CONCLUSIONS: We conclude that HSV-1716 may provide a oncolytic therapy for lung cancer even in the absence of immune system induction and a "carrier" cell could potentially deliver this vector.
