B Hu — Page 17 | Search PubMed

PubMedDate not supplied

Characterization of antitumor immunization to a defined melanoma antigen using genetically engineered murine dendritic cells.

A murine model of dendritic cell (DC)-based genetic immunization to a defined human melanoma antigen (Ag), MART-1/Melan-A (MART-1), was developed. The MART-1 gene was stably transfected into the nonimmunogenic mouse fibrosarcoma cell line NFSA that is syngeneic in C3Hf/Sem/Kam (C3H, H-2k) mice to generate the NFSA(MART1) cell line. In vivo protection from a lethal NFSA(MART1) tumor challenge could be generated by DCs transduced with a recombinant adenovirus (AdV) vector expressing MART-1 (AdVMART1). This model has the following characteristics: (a) immunological specificity and memory, (b) comparable protection for varying transduction multiplicities of infection, cell doses, and sites of DC inoculation but, interestingly, worse protection with increasing numbers of vaccinations, (c) the ability to treat small established tumors, (d) an absolute requirement for CD8 and CD4 T cells, (e) generation of MART-1-specific splenic cytotoxic T lymphocytes, and (f) up-regulation of both T helper type 1 and T helper type 2 cytokines. Genetically engineered DCs presenting defined tumor Ags represent an attractive method to generate effective immune responses.

Animals↗

PubMedDate not supplied

Kasabach-Merritt syndrome-associated kaposiform hemangioendothelioma successfully treated with cyclophosphamide, vincristine, and actinomycin D.

PURPOSE: The authors introduced a successful trial of a chemotherapy regimen to treat refractory thrombocytopenia and pain caused by a rare kaposiform hemangioendothelioma that had been refractory to corticosteroids. PATIENT AND METHOD: A 6-year-old Latina girl with diffuse petechiae, constant pain and edema in her right lower extremity, and severe thrombocytopenia was brought for treatment. Physical examination revealed a large mass in the right lower extremity. The surgical specimen resected earlier in Mexico showed kaposiform hemangioendothelioma, an extremely rare vascular tumor that is frequently associated with consumptive coagulopathy and lymphangiomatosis. Corticosteroid therapy in Mexico had been ineffective in controlling the tumor size, pain, or thrombocytopenia. The patient was brought to the United States because of a rapidly enlarging tumor and intractable leg pain, causing inability to ambulate. Laboratory examinations revealed profound thrombocytopenia and evidence of consumptive coagulopathy. Because of the rapidly enlarging lesion, it was decided to give six cycles of a chemotherapy regimen consisting of vincristine, cyclophosphamide, and actinomycin D (VAC). RESULT: The patient responded to the first cycle of chemotherapy with partial reversal of the thrombocytopenia. The additional five cycles of the same chemotherapy regimen resulted in complete resolution of thrombocytopenia and significant improvement of the pain and edema in the right lower extremity. A follow-up imaging study 9 months later revealed a marked decrease in size of the vascular tumor. CONCLUSION: Inoperable kaposiform hemangioendothelioma unresponsive to corticosteroids can be successfully treated with chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗