CDX-1307: a novel vaccine under study as treatment for muscle-invasive bladder cancer.

Abstract

Cancer vaccines have demonstrated clinical benefit, however greater efficacy could be achieved by enhancing their immunogenicity. Owing to cancer vaccines depending on uptake and cross-presentation of tumor antigens by antigen-presenting cells (APCs), we hypothesized that greater immunogenicity would accompany strategies that direct antigen to APC-expressed mannose receptors, initiating a pathway increasing class I and II presentation to T cells. CDX-1307 consists of a human monoclonal antibody targeting the mannose receptor, fused to the human chorionic gonadotropin-β chain (hCG-β), a tumor antigen frequently expressed by epithelial cancers including bladder cancer. In Phase I studies of cancer patients, CDX-1307 was well tolerated and induced significant hCG-β-specific cellular and humoral immune responses when co-administered with GM-CSF and the Toll-like receptor agonists resiquimod and poly-ICLC. An ongoing Phase II trial evaluates CDX-1307 in patients with newly diagnosed, resectable, hCG-β-expressing bladder cancer, where low tumor burden and early intervention may provide greater potential for benefit.

• Authors: Michael A Morse, Deborah A Bradley, Tibor Keler, Robert J Laliberte, Jennifer A Green, Thomas A Davis, Brant A Inman
• Journal: Expert review of vaccines (Expert Rev Vaccines) Vol. 10 Issue 6 Pg. 733-42 (Jun 2011) ISSN: 1744-8395 [Electronic] England
• PMID: 21692696 (Publication Type: Journal Article, Review)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Neoplasm
• Cancer Vaccines
• Chorionic Gonadotropin, beta Subunit, Human
• Lectins, C-Type
• Mannose Receptor
• Mannose-Binding Lectins
• Receptors, Cell Surface
• Recombinant Fusion Proteins

Topics

• Antibodies, Monoclonal (genetics, immunology)
• Antibodies, Neoplasm (blood)
• Cancer Vaccines (administration & dosage, adverse effects, immunology)
• Chorionic Gonadotropin, beta Subunit, Human (genetics, immunology)
• Clinical Trials, Phase I as Topic
• Clinical Trials, Phase II as Topic
• Humans
• Lectins, C-Type (immunology, metabolism)
• Mannose Receptor
• Mannose-Binding Lectins (immunology, metabolism)
• Muscles (pathology)
• Receptors, Cell Surface (immunology, metabolism)
• Recombinant Fusion Proteins (genetics, immunology)
• T-Lymphocytes (immunology)
• Treatment Outcome
• Urinary Bladder (pathology)
• Urinary Bladder Neoplasms (immunology, therapy)