Immune Response in Patients Diagnosed with Non-Muscle Invasive Bladder Cancer Treated with CIMAvax-EGF Concomitant with Intravesical Bacillus Calmette-Guerin

Abstract

Bladder cancer is the ninth most common malignancy worldwide and the seventh in male patients. Most of new patients are diagnosed with non-muscle invasive bladder cancer. It usually courses with a favorable prognosis, although there is a high risk of disease recurrence and progression to muscle-invasive disease. The standard treatment for intermediate and high-risk patients is a transurethral resection of bladder tumor, complemented by intravesical therapy with Bacillus Calmette-Guerin. EGFR immunoreactivity is present in about 50% of bladder cancers and correlates with recurrence, time to recurrence, and survival. Here we show the immunological results of an open, randomized, controlled, exploratory clinical trial in patients diagnosed with non-muscle invasive bladder cancer treated with CIMAvax-EGF therapeutic vaccine concomitant with intravesical BCG (n=20) or treated with intravesical BCG alone (n=24). The combination was safe and well tolerated. In vaccinated patients anti-EGF antibody titers increased during the first months of immunization and 80% of patients developed a good anti-EGF antibody response. Anti-EGF response was predominantly against the central region of the EGF molecule (loop B). IgG1 and IgG4 subclasses were the most relevant among the IgG anti-EGF antibodies generated after vaccination. The EGF serum levels were undetectable after six months of treatment. Vaccination with CIMAvax-EGF in combination with intravesical BCG develops a significant inverse correlation between anti-EGF antibody titers and baseline EGF serum concentration suggesting that in this context, the combination allowed the development of CIMAvax-EGF mechanism of action.