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. 2018 Dec 11;16(1):349.
doi: 10.1186/s12967-018-1738-6.

Tel-eVax: a genetic vaccine targeting telomerase for treatment of canine lymphoma

Joseph A Impellizeri  1 , Alessandra Gavazza  2 , Eliana Greissworth  1 , Anna Crispo  3 , Maurizio Montella  3 , Gennaro Ciliberto  4 , George Lubas  2 , Luigi Aurisicchio  5   6
Affiliations

Tel-eVax: a genetic vaccine targeting telomerase for treatment of canine lymphoma

Joseph A Impellizeri et al. J Transl Med. .

Abstract

Background: we 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).

Methods: 17 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.

Results: No 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.

Conclusions: Tel-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.

Keywords: Cancer vaccine; Canine lymphoma; Genetic vaccine; TERT.

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Figures

Fig. 1
Fig. 1
Vaccination procedure. a Vaccination schedule. Dogs received a l-CHOP 27-weeks protocol and vaccine was administered at week 4, 6 (Ad, triangles), 10, 12 and 14 (DNA–EGT, arrows). b Vet-ePorator™ device. Electroporation data are visualized in real time during pulse delivery. c DNA injection procedure. Tibialis cranialis muscle is injected with DNA, followed by electrodes insertion and application of electric field
Fig. 2
Fig. 2
Antibody detection and kinetics. a representation of the ELISA assay. Peptides are coated on the bottom of plastic wells. Incubation with dog sera and detection with a AP-conjugated anti-canine IgG allow signal detection. b Antibody detection in 12 dogs. An arbitrary threshold ∆OD405 > 0.1 was used to identify responders. c Patient 4603 and patient 6377 antibody kinetics over time
Fig. 3
Fig. 3
Kaplan–Meier estimates. Overall Survival in two Lymphoma cohorts treated with Tel-eVax™/Chemotherapy: vaccinated USA (this study) and vaccinated Italy [28]. Median survival weeks are shown
See this image and copyright information in PMC

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