China
Africa
Explore chapters and articles related to this topic
Ganglioside GD2 Specific Antibodies in the Diagnosis and Therapy of Human Neuroblastoma
Published in John T. Kemshead, Pediatric Tumors: Immunological and Molecular Markers, 2020
Nai-Kong V. Cheung, Floro D. Miraldi
In a phase I study, MAb 3F8 was given intravenously to 17 patients with metastatic, GD2 positive NB, or malignant melanoma.21 Among the eight patients with metastatic stage IV neuroblastoma, two patients (5 years and 12 years old) achieved complete bone marrow and bone remission after antibody 3F8 treatment. They both received one single dose of 3F8 and did not receive further chemotherapy or other systemic treatments. Their duration of remission were 28 weeks and 63 weeks, respectively. Although the acute side effects were significant (pain, hypertension, and urticaria), none of the patients had long-term neurological side effects or noticeable pigmentary changes. Most MAb reported to date have been primarily useful for in vitro diagnosis. When given as the native antibody to patients, the majority did not demonstrate antitumor effects.22 The ability to effect major tumor responses with a small dose of MAb is uncommon.23–24 Some have suggested that the usefulness of MAb may be best realized in patients with minimal disease. All the patients in the phase I study had gross metastatic disease, many with disease in bone and bone marrow. Nevertheless, more than one-third of them experienced tumor regression. Given the reversibility of all the side effects during treatment, the antibody 3F8 is potentially useful in the selective eradication of microscopic metastatic disease in the hope of achieving longer survival.
Clinical Studies In Oncology
Published in Siegfried Matzku, Rolf A. Stahel, Antibodies in Diagnosis and Therapy, 2019
Jan Schmielau, Wolff Schmiegel
The murine IgG3 mAb 3F8 which mediates CDC and ADCC was also raised against GD2 and applied in 17 patients with neuroblastoma or malignant melanoma (Cheung et al., 1987). The study was closed at a mAb dose of 100mg/m2 because all patients receiving this dose level developed arterial hypertension. All patients complained about pain which usually involved tumor sites and especially the abdomen, back, and extremities, independent of mAb dose. Patients with less than 1,000 U/ml HAMA, measured by ELISA, had the expected side effects as well as a therapeutic benefit from repeated infusions. Reassessment of the clinical responses (Cheung et al., 1992) revealed two PR. In a phase II trial Cheung et al. (1991) treated 16 patients with neuroblastoma. Among 13 evaluable patients one PR occurred. When patients were evaluated according to disease sites, 2 out of 7 with bone lesions and 3 out of 8 with bone marrow involvement showed tumor shrinkage (Cheung et al., 1994).
Experimental Radioimmunotherapy and Methods to Increase Therapeutic Efficacy
Published in David M. Goldenberg, Cancer Therapy with Radiolabeled Antibodies, 1995
Cheung et al.42 treated athymic nude mice bearing neuroblastoma xenografts with 125 to 1000 μCi 131I- labeled 3F8 MoAb reactive with the GD2 ganglioside present on neuroblastoma cells. There was a dose dependent inhibition of tumor growth. Complete tumor ablation was achieved with 0.5 to 1 mCi 131I- labeled 3F8. Using the MIRD technique, the dose to tumor was found to be greater than 4200 cGy. It should be emphasized that neuroblastoma is a highly radiosensitive tumor.
Natural Killer Cell-Based Cancer Immunotherapy: A Review on 10 Years Completed Clinical Trials
Published in Cancer Investigation, 2018
Wade Chun-Wai Suen, Wayne Yuk-Wai Lee, Kam-Tong Leung, Xiao-Hua Pan, Gang Li
Antibodies-conjugated cytokines can also be applied to enhance the adhesion of NK cells between tumour and NK cells: such molecules are designated immunocytokines (ICs). It is found that ICs facilitate the formation of an immune synapse between tumour and NK cells via the IL-2 receptor (IL-2R) and its α-chain takes an important role as ICs-mediated conjugation of tumour and NK cells still happened on NK cell lines with minimal expression of CD16 (170). Anti-GD2 Hu 14.18-IL-2 is a mAb that has two chimeric IL-2s attached at the Fc region of the mAb and showed improved cancer-free survival and anti-tumour response in neuroblastoma patients (171). ICs showed significant better responses than the same amount of mAb infused with cytokines simultaneously and thus it is suggested that ICs help delivers the cytokines to the site of tumours to support local NK anti-tumour effect (172). A phase 1 clinical study of anti-GD2 Hu 3F8-IL2 with allogeneic NK cells infusion in patients with high-risk neuroblastoma is currently ongoing (NCT02650648).
Adoptive immunotherapy with haploidentical natural killer cells and Anti-GD2 monoclonal antibody m3F8 for resistant neuroblastoma: Results of a phase I study
Published in OncoImmunology, 2018
Shakeel Modak, Jean-Benoit Le Luduec, Irene Y. Cheung, Debra A. Goldman, Irina Ostrovnaya, Ekaterina Doubrovina, Ellen Basu, Brian H. Kushner, Kim Kramer, Stephen S. Roberts, Richard J. O'Reilly, Nai-Kong V. Cheung, Katharine C. Hsu
Neuroblastoma (NB) comprises >8% of malignancies in children, but disproportionately accounts for 15% of all pediatric oncology deaths.1 Despite aggressive multimodality therapy, long-term progression-free survival (PFS) for high-risk (HR) NB is <50%.2 The prognosis for relapsed NB is much worse: a recent review reported 5-year post-relapse overall survival (OS) for stage 4 NB of 8%.3 Thus, newer therapies are urgently needed for metastatic and relapsed disease. NB is the first pediatric solid tumor for which monoclonal antibody (MoAb)-based immunotherapy has been proven to be effective.4 The murine anti-GD2 MoAb 3F8 (m3F8) induces complete remission (CR) in chemo-resistant osteomedullary NB,5 and improves survival in stage 4 NB patients in first6 and subsequent remissions.7 However, m3F8 is relatively ineffective against high disease burden: both osteomedullary and soft tissue.8 Furthermore, dose-intensive chemotherapy for HR-NB depletes endogenous leucocyte stores and compromises antibody-dependent cell-mediated cytotoxicity (ADCC), a major anti-NB mechanism of m3F8.
A novel multimeric IL15/IL15Rα-Fc complex to enhance cancer immunotherapy
Published in OncoImmunology, 2021
Hong Xu, Ilia N. Buhtoiarov, Hongfen Guo, Nai-Kong V. Cheung
In this manuscript, we chose GD2 and neuroblastoma as a tumor model.5 GD2 is an adhesion molecule abundantly expressed on neuroblastoma. It is also widely expressed on melanomas, small cell lung cancers, bone or soft tissue sarcomas, retinoblastomas and certain brain tumors. At least three anti-GD2 monoclonal antibodies underwent extensive clinical testing, i.e. murine 3F8 (m3F8),34 chimeric 14.18 (ch14.18, dinutuximab)35 and humanized 3F8 (naxitamab).36,37 In a phase III randomized clinical trial led by the Children’s Oncology Group, dinutuximab in combination with interleukin-2 (IL2) and GM-CSF produced a statistically significant improvement in overall survival (OS).38,39 Chimeric antigen receptor-modified effectors, e.g. anti-GD2 CART5,40 and CAR-NKT,41 are active areas of clinical investigation where cell persistence in vivo has been major challenges. As a pro-survival growth factor, IL15 is well suited to sustain adoptive NK cell and T cell immunotherapy,42 where poor effector cell persistence has been one of the major limitations. IL15/IL15Rα complex increases proliferation of both NK and CD8+/CD44high T cells in vitro and NK killing in vivo,43 suppresses established murine solid tumors,44 and induces specific anti-tumor immunity when injected intratumorally45 and in neuroblastoma, IL15 can rescue cells from M2 macrophage-induced cell death.46 Recent work using a premixed murine IL15/IL15Rα complex was also shown to enhance anti-GD2 antibody therapy in patient-derived neuroblastoma xenografts.47