Successful treatment of acute B lymphoblastic leukemia relapse in the skin and testicle by anti-CD19 CAR-T with IL-6 knocking down: a case report.

BACKGROUND: Extramedullary relapse is an important cause of treatment failure among patients with acute lymphoblastic leukemia (ALL). This type of relapse is commonly observed in the central nervous system, while it is rare in the testicles and skin. Chimeric antigen receptor-modified T cell (CAR-T) therapy targeting CD19 has shown to be a beneficial treatment approach for relapsed/refractory B cell acute lymphoblasticleukemia (r/r B-ALL). Yet, few studies have reported data regarding the treatment of extramedullary B-ALL relapse, especially both in skin and testicle, with CAR-T therapy. CASE PRESENTATION: Here we reported a single case of a patient with relapsed B-ALL in skin and testicle who was successfully treated by the shRNA-IL6-modified anti-CD19 CAR-T(ssCAR-T-19) therapy. A 29-year-old man with relapsed B-ALL in skin and testicle was enrolled in clinal trial involving the shRNA-IL6-modified anti-CD19 CAR-T(ssCAR-T-19) therapy (ClinicalTrials.gov number, NCT03919240). The patient had toxicity consistent with the grade 1 cytokine release syndrome. CONCLUSIONS: ssCART-19 therapy may be used to effectively eliminate infiltrating leukemia cells in the skin and testicle with mild toxicity, which could be a much safer approach to bridge allo-HSCT, thus further improving the patient's outcome. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT03919240, Registered 18 April 2019, retrospectively registered.

Application of alkaloids in reversing multidrug resistance in human cancers.

Multidrug resistance (MDR) in human cancer is one of greatest challenges in cancer therapy. Natural products, especially the alkaloids, exert reversed effects on MDR with low toxicity, by interacting with various targets. In this review article, we summarize the recent progress made in the research of the main alkaloids, including classification, function, mechanism, research status, and application in reversing MDR.

[Anti-tumor immune response of dendritic cells derived from lymphoma cells transduced with recombinant adenovirus encoding human P53].

This study was aimed to investigate the immunological effect of modified dendritic cells (DC) which inducing cytotoxic T cells (CTL) against lymphoma cells. The DC were isolated from the lymph node and peripheral blood of patients with diffuse large B cell lymphoma (DLBCL). DC were transfected with recombinant adenovirus vector carrying human p53 gene (rAd-p53-DC). The expression of p53 gene was detected by flow cytometry. Western-blot was used to detect the expression of P53. ELISA was used to detect IL-12 level in supernatant. The mixed lymphocyte reaction (MLR) was used to detect the proliferative ability of auto-lymphocyte stimulated by DC. The lactate dehydrogenase (LDH) release test was used to determine the cytotoxicity of CTL. The results indicates that the expressions of DC surface molecule (except for CD1a) such as CD83, CD80, CD86 and HLA-DR were significantly higher in experiment group than that in control group and blank control group. The secretion of IL-12 in supernatant was higher in experiment group than that in control group. The autologous T lymphocyte proliferation and cytotoxic activity against the same kind of DLBL-cells increased in experiment group as compared with control group and blank control group (P < 0.05). The ability to stimulate T lymphocyte proliferation increased with the rising of the ratio of DC and T lymphocyte. However, there was statistically significant difference between rAd-p53-DC derived from Lymph node and peripheral blood (P < 0.05). It is concluded that rAd-p53-transfected DC can induce CTL response in vitro against lymphoma cells.