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Exploring the pore-forming toxin aerolysin as a candidate transgene for oncolytic adenoviruses

L Moya-Borrego(1) M Costa-García(1) R Moreno(1) S Torres-Manjon(1) C Fillat(2) R Alemany(1)


Oncolytic viruses (OVs) have regained clinical interest in the oncology field for their potential to restore host anti-tumour immunity in addition to directly replicating in and killing cancer cells, making them ideal partners for combination with other immunotherapies. Among OV vector platforms, oncolytic adenoviruses are one of the most widely studied for their tumour selectivity, safety and transgene-arming capacity. However, one of the major challenges remaining is the fact that highly immunogenic viral epitopes often give rise to biased immune responses against them over tumour epitopes, a phenomenon known as viral immunodominance. Here we show that aerolysin from Aeromonas hydrophila is a strong immunogenic cell death (ICD) inducer that could enhance anti-tumour efficacy if armed in oncolytic adenoviruses. We found that vaccination with CT26 cells treated with aerolysin-containing supernatants controlled tumour growth not only in the vaccination site but also prevented a tumour rechallenge in the other flank of BALB/c mice. Thus, the absence of secondary tumour suggested that an immune response was triggered by tumour cells undergoing ICD. We expect to take benefit from aerolysin as a transgene for oncolytic therapy, taking into account that the oncolytic virus will restrict the toxicity within the tumour. Moreover, the virus-independent ICD caused by a secreted pore-forming toxin in the neighbouring non-infected cells may diminish the viral immunodominance.

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