ganglioside--gd2 and Soft-Tissue-Neoplasms

Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma. Despite aggressive therapy, patients with metastatic or relapsed disease experience dismal outcomes and novel therapies are urgently needed. In this study, we evaluated expression of disialoganglioside (GD2), a cell surface antigen with therapeutic implication, in 16 RMS patient samples. Scoring revealed GD2 positivity in 25% of the samples. These data suggest that a small subset of RMS tumors express GD2, which may be a therapeutic target in these patients.

Topics: Adolescent; Adult; Antigens, Neoplasm; Child; Child, Preschool; Female; Gangliosides; Gene Expression Regulation, Neoplastic; Humans; Infant; Infant, Newborn; Male; Rhabdomyosarcoma; Soft Tissue Neoplasms

An important component of research using animal models is ensuring rigor and reproducibility. This study was prompted after two experimenters performing virtually identical studies obtained different results when syngeneic B78 murine melanoma cells were implanted into the skin overlying the flank and treated with an in situ vaccine (ISV) immunotherapy. Although both experimenters thought they were using identical technique, we determined that one was implanting the tumors intradermally (ID) and the other was implanting them subcutaneously (SC). Though the baseline in vivo immunogenicity of tumors can depend on depth of their implantation, the response to immunotherapy as a function of tumor depth, particularly in immunologically 'cold' tumors, has not been well studied. The goal of this study was to evaluate the difference in growth kinetics and response to immunotherapy between identically sized melanoma tumors following ID versus SC implantation. We injected C57BL/6 mice with syngeneic B78 melanoma cells either ID or SC in the flank. When tumors reached 190-230 mm

Topics: Animals; Antibodies; Cancer Vaccines; Cell Line, Tumor; Female; Gangliosides; Immunotherapy; Injections, Intralesional; Interleukin-2; Kinetics; Melanoma; Mice, Inbred C57BL; Neoplasm Transplantation; Recombinant Fusion Proteins; Skin Neoplasms; Soft Tissue Neoplasms; Transplantation, Isogeneic; Tumor Burden; Vaccination

Early and correct diagnosis of local tumor recurrence, occurrence of metastases, and therapy response are essential in patients with neuroblastoma stage IV. The aim of the study was to evaluate the diagnostic value of metaiodobenzylguanidine (mIBG) and a chimeric GD2 antibody in the follow-up of patients with neuroblastoma. In a prospective study, mIBG (N = 31 scans) and immunoscintigraphy were compared with a chimeric antiganglioside antibody, ch14.18 (MAb) (N = 31 scans), labeled with technetium Tc 99m in the follow-up of 18 patients with stage IV neuroblastoma. The findings were compared with histologic findings, other imaging examinations, and clinical changes over the course of 4 to 6 years. For the diagnosis of local tumor recurrences, sensitivity was 80% for MAb and 70% for mIBG. Specificity was 93% for MAb and 72% for mIBG. The MAb was superior for the detection of skeletal metastases, with a sensitivity of 82% compared with 72% for mIBG. Specificity was 100% for both techniques. Also, for soft tissue/lymph node metastases, sensitivity for MAb was higher (50%) than for mIBG (31%). Specificity was 100% for each technique. In sequential studies, metastases were detected earlier with MAb (mean: 2.3 m for skeletal metastases, 3.6 m for soft tissue metastases) than with mIBG. After therapy, tumor uptake was visualized longer with mIBG (mean 6.3 m) than with MAb. The chimeric antibody ch14.18 is likely to be valuable for follow-up examinations and for assessment of therapy response because of earlier detection of new metastases.

Topics: 3-Iodobenzylguanidine; Adolescent; Antibodies, Monoclonal; Bone Neoplasms; Child; Child, Preschool; False Negative Reactions; Female; Fluorescent Antibody Technique; Follow-Up Studies; Gangliosides; Humans; Liver Neoplasms; Male; Neoplasm Recurrence, Local; Neoplasm Staging; Neuroblastoma; Radionuclide Imaging; Radiopharmaceuticals; Recombinant Fusion Proteins; Soft Tissue Neoplasms; Technetium

Fifty-six freshly frozen human sarcomas were studied for expression of disialogangliosides by avidin-biotin immunohistochemical staining with purified monoclonal antibodies (MoAb) 3F8 (antidisialoganglioside GD2) and R24 (antidisialoganglioside GD3).. Ninety-three percent of the tumors tested by the immunohistochemical staining expressed GD2 and 88% expressed GD3. The intensity of expression varied among sarcomas of different histologic types. Liposarcoma, fibrosarcoma, malignant fibrous histiocytoma, leiomyosarcoma, and spindle cell sarcoma reacted strongly with 3F8 and R24. Embryonal rhabdomyosarcoma and synovial sarcoma demonstrated substantially weaker staining by either MoAb. Weakly reactive or nonreactive tumors were, in general, high-grade or metastatic sarcomas. Ganglioside extraction and thin-layer chromatography/immunothin-layer chromatography of two liposarcomas confirmed the identities of these gangliosides.. GD2 and GD3 may indicate sites for MoAb-targeted imaging and therapy for sarcomas. The association of a diminished stainability by 3F8 and R24 with aggressive sarcomas may indicate prognostic significance.

Topics: Gangliosides; Humans; Immunoenzyme Techniques; Sarcoma; Soft Tissue Neoplasms