Clinical development and Perspectives of CImAvax EgF, Cuban Vaccine for Non-small-cell Lung Cancer therapy

Introduction CIMAvax EGF is a therapeutic anticancer vaccine de- veloped entirely in Cuba and licensed in Cuba for use in adult patients with stage IIIB/IV non-small-cell lung cancer (NSCLC). The vaccine is based on active immunotherapy by which an individual's immune response is manipulated to release its own effector antibodies (Abs) against the epidermal growth factor (EGF). Results Articles reviewed describe five phase I/II and one phase II clinical trials conducted in Cuba in 1995-2005. A non-controlled 1995-1996 study resulted in the earliest published scientific evidence of the feasibility of inducing an immune response against autologous EGF in patients with different advanced stage tumors. Subsequent controlled, randomized trials included patients with advanced stage (IIIB/IV) NSCLC. The 2nd and 3rd phase I/II trials differentiated immunized patients as poor antibody responders (PAR) and good antibody responders (GAR), according to their anti-EGF antibody response, and confirmed greater immunogenicity with Montanide ISA 51 adjuvant in the vaccine formulation, as well as the benefits of low-dose cyclophosphamide treatment 72 hours before the first immunization. The 4 th phase I/II trial found increased immunogenicity with an increased dose divided in 2 anatomical sites and also established correlation between Ab titers, serum EGF concentration and length of survival. In the first 4 phase I/II trials and the phase II trial, vaccine was administered after chemotherapy (ChTVV schedule). In the 5 th phase I/II trial, longer survival and increased immunogenicity were achieved using a VChTV schedule and dividing the vaccine dose in 4 anatomical sites. The phase II clinical trial confirmed results of earlier studies as well as the mild- to-moderate adverse event profile associated with CIMAvax EGF. Longer survival was observed in all vaccinated patients compared to controls, and the difference was significant (p <0.05) in the group aged <60 years. Conclusions CIMAvax EGF's benefits in earlier NSCLC stages and in other tumor locations, as well as in patients unfit for chemotherapy, need to be evaluated. Evidence of the vaccine's safety for chronic use also needs to be systemized.