Highlights on endoglin (CD105): from basic findings towards clinical applications in human cancer

Antibody targeting of tumor-associated vasculature is a promising therapeutic approach in human cancer; however, a specific cell membrane marker for endothelial cells of tumor vasculature has not been discovered yet. Endoglin (CD105) is a cell-surface glycoprotein most recently identified as an optimal indicator of proliferation of human endothelial cells. The finding that CD105 is over-expressed on vascular endothelium in angiogenetic tissues has prompted several pre-clinical studies designed to get a deeper understanding on the role of CD105 in angiogenesis, and to evaluate the most appropriate clinical setting(s) to utilize CD105 as a therapeutic target. In this review, the foreseeable clinical applications of CD105 in human cancer are discussed

Optimizing complement-activating antibody-based cancer immunotherapy: a feasible strategy?

Passive immunotherapy with monoclonal antibodies (mAb) targeted to specific tumor-associated antigens is amongst the most rapidly expanding approaches to biological therapy of cancer. However, until now a limited number of therapeutic mAb has demonstrated clinical efficacy in selected neoplasia. Results emerging from basic research point to a deeper characterization of specific biological features of neoplastic cells as crucial to optimize the clinical potential of therapeutic mAb, and to identify cancer patients who represent the best candidates to antibody-based immunotherapy. Focus on the tissue distribution and on the functional role of membrane complement-regulatory proteins such as Protectin (CD59), which under physiologic conditions protects tissues from Complement (C)-damage, might help to optimize the efficacy of immunotherapeutic strategies based on C-activating mAb

The Italian Network for Tumor Biotherapy (NIBIT): Getting together to push the field forward

As for a consolidated tradition, the 5th annual meeting of the Italian Network for Cancer Biotherapy took place in the Certosa of Pontignano, a Tuscan monastery, on September 20–22, 2007. The congress gathered more than 40 Italian leading groups representing academia, biotechnology and pharmaceutical industry. Aim of the meeting was to share new advances in cancer bio-immunotherapy and to promote their swift translation from pre-clinical research to clinical applications. Several topics were covered including: a) molecular and cellular mechanisms of tumor escape; b) therapeutic antibodies and recombinant constructs; c) clinical trials up-date and new programs; d) National Cooperative Networks and their potential interactions; e) old and new times in cancer immunology, an "amarcord". Here, we report the main issues discussed during the meeting

Tremelimumab for patients with chemotherapy-resistant advanced malignant mesothelioma: an open-label, single-arm, phase 2 trial

Background Monoclonal antibodies (mAb) to cytotoxic T-lymphocyte antigen 4 (CTLA4) have shown therapeutic activity in different tumour types. We aimed to investigate the efficacy, safety and immunological activity of the anti-CTLA4 mAb, tremelimumab, in advanced malignant mesothelioma (MM). Methods This open-label, single-arm phase 2 study enrolled patients 18 years or older with measurable, unresectable MM and progressive disease (PD) after a first-line platinum-based regimen between May 27, 2009, and January 10, 2012. Eligible patients had a life expectancy of 3 months or more, an Eastern Cooperative Oncology Group performance status of 2 or less, and no history of autoimmune diseases. Treatment comprised tremelimumab 15 mg/kg intravenously once every 90 days until PD or severe toxicity. The primary endpoint was the proportion of patients who achieved an objective response according to the modified Response Evaluation Criteria in Solid Tumors (RECIST) for pleural MM or RECIST for peritoneal MM.. Analyses were done per intention to treat. This trial is registered with EudraCT, number 2008-005171-95, and with ClinicalTrials.gov, number NCT01649024. Findings Twenty-nine patients with MM were enrolled, of median age 64 (47–77) years, ECOG performance status 0-2, with stage III (n=11) or IV (n=18) disease. All patients received at least one dose of tremelimumab (median 2; range 1–9). The study did not reach its primary endpoint; however, two patients experienced durable (6 and 15+ months) partial response (PR); one PR occurred after initial PD. Grade 3 or 4 AEs, seen in four patients (14%), comprised gastrointestinal (n=2), neurological (n=1), hepatic (n=2) and pancreatic (n=1) toxicity. Interpretation The limited number of patients enrolled in this non-randomized study requires to interpret the results with caution; nevertheless, tremelimumab promises to have encouraging clinical activity in pre-treated patients with advanced MM, with potential to impact on survival and an acceptable safety and tolerability profile. Funding Associazione Italiana per la Ricerca sul Cancro, Istituto Toscano Tumori, Pfizer Inc., and Fondazione Buzzi Unice