Abstract
Backgroundwe have recently shown that Tel-eVax, a genetic vaccine targeting dog telomerase (dTERT) and based on Adenovirus (Ad)/DNA Electro-Gene-Transfer (DNA–EGT) technology can induce strong immune response and increase overall survival (OS) of dogs affected by multicentric Diffuse Large B cell Lymphoma (DLBCL) when combined to COP therapy in a double-arm study. Here, we have utilized a clinically validated device for veterinary electroporation called Vet-ePorator™, based on Cliniporator™ technology currently utilized and approved in Europe for electrochemotherapy applications and adapted to electrogenetransfer (EGT).Methods17 dogs affected by DLBCL were vaccinated using two Ad vector injections (Prime phase) followed by DNA–EGT (Boost phase) by means of a Vet-ePorator™ device and treated in the same time with a 27-week Madison Wisconsin CHOP protocol. The immune response was measured by ELISA assays using pool of peptides.ResultsNo significant adverse effects were observed. The OS of vaccine/CHOP animals was 64.5 weeks, in line with the previous study. Dogs developed antibodies against the immunizing antigen.ConclusionsTel-eVax in combination with CHOP is safe and immunogenic in lymphoma canine patients. These data confirm the therapeutic efficacy of dTERT vaccine and hold promise for the treatment of dogs affected by other cancer types. More importantly, our findings may translate to human clinical trials and represent new strategies for cancer treatment.
Highlights
Lymphoma is one of the most common malignancies diagnosed in pet dogs in the United States [1, 2]
We have recently shown that Tel-eVax, a genetic vaccine based on Adenovirus (Ad) and DNA Electro-Gene-Transfer (DNA–EGT) and targeting dTERT was able to induce strong immune response in dogs affected by B-cell LSA
In two previous studies [33, 34], we have shown that Tel-eVax is safe, immunogenic and most importantly had a significant therapeutic impact on Diffuse Large B-cell Lymphoma (DLBCL) dogs when combined with COP. dTERT-specific cell mediated immune responses were induced in almost all treated animals
Summary
Lymphoma is one of the most common malignancies diagnosed in pet dogs in the United States [1, 2]. Among these canine lymphoma accounts for up to 24% of all reported neoplasms and the majority (60–80%) arises from malignant B cells. Immunochemotherapy with rituximab and CHOP (R-CHOP) is the current first-line treatment [17] With this therapeutic approach up to 40% of patients experience early treatment failure or relapse after initial response [18]. Considering the average life span of dogs and humans (about sevenfold difference), this further confirms the high translational relevance of canine patients in Comparative Oncology initiatives
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