The mechanism of N-acetylcysteine photoprotection is not related to dipyrimidine photoproducts

Topical application of N-acetylcysteine prior to UVB irradiation of BALB/c mice has previously been shown to inhibit systemic suppression of the contact hypersensitivity response. Formation of cis-urocanic acid, however, is not affected. Besides urocanic acid, UV-induced DNA damage has been held responsible for the initiation of suppression of the contact hypersensitivity response. Therefore, the possible inhibitory effect of N-acetylcysteine on UVB-induced cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidone photoproducts has been investigated. No effect on the photoproducts studied is observed, suggesting that N-acetylcysteine exerts its photoprotective effect during the post-initiation phase of photoimmunosuppression

Complement-dependent cytotoxicity induced by therapeutic antibodies in B-cell acute lymphoblastic leukemia is dictated by target antigen expression levels and augmented by loss of membrane-bound complement inhibitors

Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease

A mechanistic rationale for combining alemtuzumab and rituximab in the treatment of ALL

B-lineage acute lymphoblastic leukemia (ALL) may express CD52 and CD20. Alemtuzumab (ALM) and rituximab (RTX) are therapeutic antibodies directed against CD52 and CD20, respectively, but showed limited activity against ALL in clinical trials. The mechanisms for the impaired responses remained unclear. We studied expression of CD52 and CD20 on ALL cells and found that most cases coexpressed CD52 and CD20. However, distinct CD52-negative (CD52(-)) subpopulations were detected in most cases as the result of defective glycophosphatidyl-inositol anchoring. Although ALM efficiently eradicated CD52-positive (CD52(+)) cells in NOD/scid mice engrafted with primary human ALL, CD52(-) subclones escaped therapy. In the same model, RTX showed limited activity resulting from occurrence of CD20 down-modulation. However, CD52(-) cells concurrently lacked the glycophosphatidyl-inositol-anchored complement regulators CD55 and CD59 and showed increased susceptibility to RTX-mediated complement-dependent cytotoxicity in vitro. At the same time, ALM was shown to inhibit down-modulation of CD20 in response to RTX by depleting the trogocytic capacity of phagocytic cells. Probably because of these complementary mechanisms, combined administration of ALM and RTX induced complete responses in vivo. Based on these data, we propose a mechanistic rationale for combined application of RTX and ALM in ALL. (Blood. 2010;116(26):5930-5940)Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease

Human allo-reactive CD4+T cells as strong mediators of anti-tumor immunity in NOD/scid mice engrafted with human acute lymphoblastic leukemia

Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease