Cancer
Radioimmunotherapy of non‐Hodgkin lymphoma comprises a 90Y‐ or 131I‐labeled murine anti‐CD20 IgG, but both agents also include a substantial dose of unlabeled anti‐CD20 IgG given immediately before the radioconjugate to reduce its uptake in the spleen (primary normal B‐cell antigen sink); this extends its plasma half‐life and improves tumor visualization. Thus, these treatments combine an effective...
FMS‐related tyrosine kinase receptor 3 (FLT3) is a class III receptor tyrosine kinase that holds considerable promise as a therapeutic target in hematologic malignancies. Current efforts directed toward the development of small‐molecule tyrosine kinase inhibitors of FLT3 may be limited by off‐target toxicities and the development of drug resistance. Target‐specific antibodies could overcome these...
This supplement includes 16 representative articles presented at the 12th Conference on Cancer Therapy With Antibodies and Immunconjugates, Parsippany, New Jersey, October 16‐18, 2008, encompassing cancer treatment with unconjugated and isotope‐conjugated antibodies targeting selective cancer biomarkers. Cancer 2010;116(4 suppl):1011–2. © 2010 American Cancer Society.
BACKGROUND:Antibody‐drug conjugates, comprising monoclonal antibodies (MoAbs) that bind to tumor‐associated antigens, display different toxicity profiles compared with radiolabeled MoAbs. Dose‐limiting toxicities may include damage to the liver and myelotoxicity. The drug component is the antimitotic agent auristatin, which is 100‐1000 times more potent than doxorubicin. Consequently, auristatin antibody‐drug...
A large body of evidence suggests that the platelet‐derived growth factor (PDGF) family and associated receptors are potential targets in oncology therapeutic development because of their critical roles in the proliferation and survival of various cancers and in the regulation and growth of the tumor stroma and blood vessels. Several small molecules that nonspecifically target the PDGF signaling axis...
BACKGROUND:Antibody‐based imaging agents are available commercially, but their success has been limited, mainly because of low contrast and the emergence of 2‐fluoro‐2‐deoxy‐D‐glucose‐positron emission tomography (FDG‐PET) scanning. In pretargeting, administration of the radionuclide is separated from the antibody, thereby enhancing image contrast and allowing detection at earlier time points after...
Approximately 66,000 Americans develop non‐Hodgkin lymphoma (NHL) each year. Although the use of unlabeled antibodies such as rituximab has significantly improved survival when combined with standard chemotherapy regimens, approximately two‐thirds of lymphoma patients eventually develop disease recurrence and die of their disease. Novel treatments are urgently needed to cure these patients. One strategy...
The human vascular endothelial growth factor receptor‐1 (VEGFR‐1, or Flt‐1) is widely expressed in normal and pathologic tissue and contributes to the pathogenesis of both neoplastic and inflammatory diseases. In human cancer, VEGFR‐1 mediated signaling is responsible for both direct tumor activation and angiogenesis. VEGFR‐1 mediated activation of nonmalignant supporting cells, particularly stromal,...
BACKGROUND:Pretargeting is an approach for enhancing the therapeutic index of radioimmunotherapy by separating the administrations of tumor‐targeting substance and radiolabel. In this study, a pretargeting model system of avidin‐conjugated monoclonal antibody trastuzumab and biotinylated, 211At‐labeled poly‐L‐lysine was constructed and analyzed in vitro.
METHODS:Avidin activated by 4‐(N‐maleimidomethyl)cyclohexane‐1‐carboxylic...
Despite recent advances, advanced prostate cancer is suboptimally responsive to current chemotherapeutic agents. Radiolabeled monoclonal antibody therapy that targets prostate‐specific membrane antigen (PSMA) shows promise and is an area of active investigation. J591 is a deimmunized IgG monoclonal antibody developed to target the extracellular domain of PSMA. Preclinical and early phase clinical...
Medullary thyroid cancer (MTC) patients with localized residual disease and/or distant metastases may survive for several years or rapidly progress and die of their disease. Thus, highly reliable prognostic factors are needed for an early distinction between high‐risk patients who need to be treated and low‐risk patients who warrant a watch‐and‐wait approach. Calcitonin doubling time is an independent...
BACKGROUND:Human papillomavirus (HPV) infection is considered a necessary step for the development of cervical cancer, and >95% of all cervical cancers have detectable HPV sequences. The authors of this report recently demonstrated the efficacy of radioimmunotherapy (RIT) targeting viral oncoprotein E6 in the treatment of experimental cervical cancer. They hypothesized that the pretreatment of...
BACKGROUND:Human epidermal growth factor receptor–2 (HER‐2) and tumor‐associated glycoprotein 72 (TAG‐72) have proven to be excellent molecular targets for cancer imaging and therapy. Trastuzumab, which binds to HER‐2, is effective in the treatment of disseminated intraperitoneal disease when labeled with 213Bi or 212Pb. 213Bi‐humanized CC49 monoclonal antibody (HuCC49ΔCH2), which binds to TAG‐72,...
BACKGROUND:Significant antitumor effects were previously observed with radioimmunotherapy (RIT) using an anti‐carcinoembryonic antigen (CEA) monoclonal antibody (F6) labeled with iodine‐131 in medullary thyroid cancer (MTC)‐bearing nude mice. Nevertheless, no complete response was achieved. Because angiogenesis is critical for tumor growth, bevacizumab is used to treat solid tumor in clinical practice...
BACKGROUND:The aim of the current study was to investigate the possibility of increasing the maximal tolerated dose (MTD) of a tumor‐selective radiolabeled antibody when radioimmunotherapy (RIT) is combined with extracorporeal depletion of radioimmunoconjugates from the circulation. Furthermore, the authors evaluated whether this increase in dose improved the therapeutic effect on solid manifest tumors...
BACKGROUND:Maximum injected activity in radioimmunotherapy (RIT) is limited by bone marrow toxicity. Many dosimetric approaches have been proposed, leading to high variability in the results and elusive absorbed dose‐effect relations. This study presents the results of red marrow (RM) absorbed dose estimates performed with 3 methods.
METHODS:Five patients received 2 co‐infusions of 90Y‐labeled (370...
BACKGROUND:177Lu‐(DOTA0,Tyr3) octreotate is a new treatment modality for disseminated neuroendocrine tumors. According to a consensus protocol, the calculated maximally tolerated absorbed dose to the kidney should not exceed 27 Gy. In commonly used dosimetry methods, planar imaging is used for determination of the residence time, whereas the kidney mass is determined from a computed tomography (CT)...
BACKGROUND:The 2 closely related small GTPases, RHOC and RHOA, are involved in mammary gland carcinogenesis; however, their specific roles in determining cancer cell adhesion and invasion have not been elucidated.
METHODS:RHOA and RHOC are highly homologous, thereby posing a major challenge to study their individual functions in cancer cells. By selectively knocking down these proteins, we have been...