Cancer

This supplement includes 16 representative articles presented at the 12^th 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.

FMS-related tyrosine kinase receptor 3 (FLT3)-directed agents hold considerable promise in hematologic malignancies. IMC-EB10, a fully human monoclonal antibody targeting FLT3, was active in leukemia preclinical models and was the first antibody to enter clinical development in this setting.

The platelet-derived growth factor (PDGF)/PDGF receptor α (PDGFRα) signaling axis is a rational target for anticancer therapeutic development, because it plays a critical role in cancer growth, survival, and metastasis and in modulation of the stromal and angiogenic support for cancer growth. This article reviews the rationale for targeting the PDGF/PDGFRα signaling axis and focuses on IMC-3G3, a fully human immunoglobulin G subclass 1 antibody that targets PDGFRα. IMC-3G3 is undergoing early clinical development as an anticancer therapeutic.

Vascular endothelial growth factor receptor-1 (VEGFR-1) mediated signaling contributes to cancer pathogenesis by means of both direct growth stimulation and activation of endothelial, stromal, progenitor, and other cells. Antibody-mediated inhibition of VEGFR-1 represents a promising anti-cancer strategy and preliminary clinical studies investigating IMC-18F1 in humans indicate a favorable safety profile.

Extracorporeal affinity adsorption treatment can be used to reduce the toxicity associated with administration of monomethylauristatin FBR96 conjugates, making it possible to increase the amount of conjugates administered.

Extracorporeal affinity adsorption treatment allows increased administered activity without increased toxicity, with the aim of increasing the absorbed dose to the tumor. Because tumor/normal tissue radiosensitivity ratios are more favorable in rodents, it is not possible to draw any conclusions concerning the therapeutic efficacy of increased administered activity.

A pretreatment with bevacizumab may improve radioimmunotherapy efficacy and offer acceptable toxicity in medullary thyroid carcinoma.

The authors investigated the potential of targeting 2 distinct molecules in tumors with high linear energy transfer radioimmunotherapy for the management and treatment of cancer patients who presented with disseminated peritoneal disease. The intent of developing a treatment regimen using α-targeted radiation was to expand the therapeutic repertoire to patient populations beyond those with pancreatic or ovarian cancer to patients with cancers of the colon, stomach, and small intestine, which result in peritoneal carcinomatosis, and to patients with peritoneal mesothelioma.

The efficacy of radioimmunotherapy (RIT) targeting viral oncoprotein E6 in the treatment of human papillomavirus (HPV) type 16 (HPV‒16)-related and HPV18-related cervical cancer would depend on the level and accessibility of intranuclear E6 protein in the tumor. The authors demonstrated that pretreatment of CasKi HPV16-positive tumors in mice with proteasome inhibitor MG132 significantly increased the uptake of radiolabeled anti-E6 antibody in the tumor and cleared quickly from all normal tissues.

J591 is a deimmunized monoclonal antibody against prostate-specific membrane antigen. Radiolabeled J591 has been demonstrated to have excellent targeting of prostate cancer metastases, is well tolerated, and has clinical efficacy.

Three different methods were used to evaluate the absorbed dose to the kidneys in patients with disseminated neuroendocrine tumors treated with ¹⁷⁷Lu-(DOTA0,Tyr3) octreotate. Dosimetry based on planar images generally gave higher absorbed dose values compared with methods including single-photon emission computed tomography (SPECT) data. Two different SPECT-based methods gave similar values, although the calculations were based on different assumptions.

This study shows that image-based red marrow absorbed dose determination is useful to predict hematological toxicity in NHL patients treated with ⁹⁰Y-labeled epratuzumab.

A full scale avidin-biotin pretargeting system was evaluated in vitro, showing high binding of pretargeting molecule to tumor cells, as well as high binding of effector molecule to pretargeted tumor cells.

In an open-label, single-arm trial that assessed a pretargeting procedure for diagnostic imaging of carcinoembryonic antigen-expressing colorectal cancer, the best imaging results were produced 24 hours after ¹¹¹In-labeled peptide administration using a 4-day interval between injection of the bispecific antibody and the peptide.

Currently there is no approved drug for the systemic treatment of patients with rapidly progressing metastatic medullary thyroid carcinoma. Pretargeted radioimmunotherapy has been the only innovative treatment modality convincingly showing some survival benefit in such patients.

Radioimmunotherapy (RIT) has emerged as a valid treatment strategy for lymphoma patients based on the favorable results of a growing number of clinical trials. Various approaches designed to further improve effectiveness and reduce toxicity of RIT are summarized in this review.

Radioimmunotherapy is a safe and effective treatment of non-Hodgkin lymphoma that combines an anti-CD20 IgG radioconjugate with a large amount of unlabeled anti-CD20 antibody intended to allow the radioimmunoconjugate to bypass the CD20 antigen sink, but in excess, it could compromise the efficacy of the radioconjugate. Other approaches, such as combining anti-CD20 antibody therapy with radioimmunoconjugate that binds to another B-cell specific antigen, can enhance responses, or in the case of pretargeting procedures with consolidation anti-CD20 antibody therapy, enhance responses with reduced toxicity.