Clinical immunotherapeutic approaches for the treatment of head and neck cancer.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, accounting for more than 550,000 cases and 380,000 deaths annually. The primary risk factors associated with HNSCC are tobacco use and alcohol consumption; nevertheless genetic predisposition and oncogenic viruses also play important roles in the development of these malignancies. The current treatments for HNSCC patients include surgery, chemotherapy, radiotherapy, and cetuximab, and combinations of these. However, these treatments are associated with significant toxicity, and many patients are either refractory to the treatment or relapse after a short period. Despite improvements in the treatment of patients with HNSCC, the clinical outcomes of those who have been treated with standard therapies have remained unchanged for over three decades and the 5-year overall survival rate in these patients remains around 40-50%. Therefore, more specific and less toxic therapies are needed in order to improve patient outcomes. The tumour microenvironment of HNSCC is immunosuppressive; therefore immunotherapy strategies that can overcome the immunosuppressive environment and produce long-term tumour immunosurveillance will have a significant therapeutic impact in these patients. This review focuses on the current immunological treatment options under investigation or available for clinical use in patients with HNSCC.

An immunologically relevant rodent model demonstrates safety of therapy using a tumour-specific IgE.

BACKGROUND: Designing biologically informative models for assessing the safety of novel agents, especially for cancer immunotherapy, carries substantial challenges. The choice of an in vivo system for studies on IgE antibodies represents a major impediment to their clinical translation, especially with respect to class-specific immunological functions and safety. Fcε receptor expression and structure are different in humans and mice, so that the murine system is not informative when studying human IgE biology. By contrast, FcεRI expression and cellular distribution in rats mirror that of humans. METHODS: We are developing MOv18 IgE, a human chimeric antibody recognizing the tumour-associated antigen folate receptor alpha. We created an immunologically congruent surrogate rat model likely to recapitulate human IgE-FcεR interactions and engineered a surrogate rat IgE equivalent to MOv18. Employing this model, we examined in vivo safety and efficacy of antitumour IgE antibodies. RESULTS: In immunocompetent rats, rodent IgE restricted growth of syngeneic tumours in the absence of clinical, histopathological or metabolic signs associated with obvious toxicity. No physiological or immunological evidence of a "cytokine storm" or allergic response was seen, even at 50 mg/kg weekly doses. IgE treatment was associated with elevated serum concentrations of TNFα, a mediator previously linked with IgE-mediated antitumour and antiparasitic functions, alongside evidence of substantially elevated tumoural immune cell infiltration and immunological pathway activation in tumour-bearing lungs. CONCLUSION: Our findings indicate safety of MOv18 IgE, in conjunction with efficacy and immune activation, supporting the translation of this therapeutic approach to the clinical arena.