Targeted alpha therapy with 212Pb-NNV003 for the treatment of CD37 positive B-cell chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL)

354Background: Each year more than 90,000 cases of chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL) are expected in the US. The standard of care includes immuno-chemotherapy with alkylating agents in combination with an anti-CD20 monoclonal antibody, in addition to targeted therapies such as Bruton’s tyrosine kinase inhibitors. While immuno-chemotherapy regimens are initially effective in inducing responses, most patients inevitably relapse and the same therapies show decreasing efficacy with repeated administration. In recent years, CD37 has emerged as a new therapeutic target for B-cell malignancies. CD37 is highly and selectively expressed on the surface of mature B lymphocytes and B-cell malignancies. Therapies targeting CD37-expressing cells may become a useful alternative to CD20 targeting agents, due to the emergence of resistance to anti-CD20 therapies over time. Alpha-emitting radionuclides have demonstrated good potential for cancer targeted therapies because of efficient energy deposition along the short alpha track (50-100 µm). The absorbed energy causes irreparable DNA double-strand breaks and localized cytotoxicity while sparing surrounding healthy tissues. We have developed a targeted alpha therapy (TAT) where the CD37-specific antibody NNV003 is coupled to the alpha-particle-emitting radioisotope 212Pb. We recently showed that 212Pb-NNV003 is highly effective in animal models of Burkitt’s lymphoma and CLL (Saidi et al., Blood...
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Oncology, Basic and Translational (Basic Science) III Source Type: research

Related Links:

Sialyl Lewis A (sLeA, also known as CA19-9), a tetrasaccharide selectively and highly expressed on advanced adenocarcinomas including colon, stomach, and pancreatic cancers, has long been considered as an attractive target for active and passive vaccination. While progress in antibodies targeting tumor-associated protein antigens resulted in an impressive array of therapeutics for cancer treatment, similar progress in exploiting tumor-associated carbohydrate antigens, such as sLeA, has been hampered by the lack of a detailed understanding of the singular characteristics of these antigens. We have addressed this issue by an...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Despite recent therapeutic advances, prostate cancer remains a leading cause of cancer-related death. A subset of castration-resistant prostate cancers become androgen receptor (AR) signaling independent and develop neuroendocrine prostate cancer (NEPC) features through lineage plasticity. These NEPC tumors, associated with aggressive disease and poor prognosis, are driven, in part, by aberrant expression of N-Myc, through mechanisms that remain unclear. Integrative analysis of the N-Myc transcriptome, cistrome, and interactome using in vivo, in vitro, and ex vivo models (including patient-derived organoids) identified a l...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Induction of memory CD8+ T cells is important for controlling infections such as malaria and HIV/AIDS and for cancer immunotherapy. Accurate assessment of antigen-specific (Ag-specific) CD8+ T cells is critical for vaccine optimization and for defining correlates of protection. However, conditions for determining Ag-specific CD8+ T cell responses ex vivo using intracellular cytokine staining (ICS) may be variable, especially in humans with complex antigens. Here, we used an attenuated whole parasite malaria vaccine model in humans and various experimental infections in mice to show that the duration of antigenic stimulatio...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
New J. Chem., 2019, Accepted Manuscript DOI: 10.1039/C9NJ03653A, PaperHuiping Wang, Libang He, Peng Zhang, Jie Zhang, Zhenhua Chen, Xiuli Ren, Xifan Mei Targeted delivery of therapeutic drug into cancer cells is a facile method to improve the therapeutic efficacy. Focused on this point, the doxorubicin (DOX) -loaded hydroxyapatite (HAP) nanorods consisting of... The content of this RSS Feed (c) The Royal Society of Chemistry
Source: RSC - New J. Chem. latest articles - Category: Chemistry Authors: Source Type: research
Chem. Commun., 2019, Accepted Manuscript DOI: 10.1039/C9CC05826E, CommunicationJia Li, Le Li Zeng, Kai Xiong, Thomas Wheildon Rees, Chengzhi Jin, Weijun Wu, Yu Chen, Liangnian Ji, Hui Chao Platinum-resistant cancer cells are sensitive to changes in the levels of reactive oxidative species (ROS). Herein, we design a biotin-modified Ru(II) complex as photosensitizer (denoted as Ru-Biotin). Ru-Biotin can selectively... The content of this RSS Feed (c) The Royal Society of Chemistry
Source: RSC - Chem. Commun. latest articles - Category: Chemistry Authors: Source Type: research
Chem. Commun., 2019, Accepted Manuscript DOI: 10.1039/C9CC03379C, CommunicationAnnemiek Uvyn, Ruben De Coen, Olivier De Wever, Kim Deswarte, Bart Lambrecht, Bruno De Geest Triggering antibody-mediated innate immune mechanisms to kill cancer cells is an attractive therapeutic avenue. In this context, recruitment of endogenous antibodies to the cancer cell surface could be a viable... The content of this RSS Feed (c) The Royal Society of Chemistry
Source: RSC - Chem. Commun. latest articles - Category: Chemistry Authors: Source Type: research
Publication date: Available online 19 August 2019Source: The American Journal of SurgeryAuthor(s): Katherine Bingmer, Asya Ofshteyn, David Dietz, Sharon L. Stein, Emily SteinhagenAbstractBackgroundImmunosuppressed patients have an increased risk of developing anal cancer, but little data exists regarding outcomes of this population.MethodsA retrospective review of anal cancer patients at a single academic institution from 2006-2017 was performed.Results19 (14%) of 136 anal cancer patients were immunosuppressed. Immunosuppressed patients were more likely to be hypoalbuminemic (21% vs. 6%, p=0.025), less likely to complete c...
Source: The American Journal of Surgery - Category: Surgery Source Type: research
ConclusionsAbdominal wall defects from resection of cancerous masses of the abdominal wall can be closed with a contralateral rectus abdominis muscle transplant in the absence of mesh.
Source: International Journal of Surgery Case Reports - Category: Surgery Source Type: research
Source: Radiologia Brasileira - Category: Radiology Source Type: research
ConclusionThe results of preclinical studies suggest that TAT using 212Pb-NNV003 is a safe and effective method for the treatment of CD37 positive CLL and NHL.DisclosuresSaidi: Orano Med: Employment. Maaland: Nordic Nanovector: Employment. Torgue: Orano Med: Employment, Membership on an entity's Board of Directors or advisory committees. Heyerdahl: Nordic Nanovector: Employment, Equity Ownership. Dahle: Nordic Nanovector ASA: Employment, Equity Ownership, Patents &Royalties.
Source: Blood - Category: Hematology Authors: Tags: 642. CLL: Therapy, excluding Transplantation: Poster III Source Type: research
More News: Burkitt Lymphoma | Cancer | Cancer & Oncology | Chemotherapy | Chronic Leukemia | Chronic Lymphocytic Leukemia | Clinical Trials | Erbitux | Leukemia | Lymphoma | Non-Hodgkin's Lymphoma | Nuclear Medicine | Science | Statistics | Study