Abstract
The Newcastle disease virus (NDV) strain AF2240 is an avian avulavirus that has been demonstrated to possess oncolytic activity against cancer cells. However, to illicit a greater anti-cancer immune response, it is believed that the incorporation of immunostimulatory genes such as IL12 into a recombinant NDV backbone will enhance its oncolytic effect. In this study, a newly developed recombinant NDV that expresses IL12 (rAF-IL12) was tested for its safety, stability and cytotoxicity. The stability of rAF-IL12 was maintained when passaged in specific pathogen free (SPF) chicken eggs from passage 1 to passage 10; with an HA titer of 29. Based on the results obtained from the MTT cytotoxic assay, rAF-IL12 was determined to be safe as it only induced cytotoxic effects against normal chicken cell lines and human breast cancer cells while sparing normal cells. Significant tumor growth inhibition (52%) was observed in the rAF-IL12-treated mice. The in vivo safety profile of rAF-IL12 was confirmed through histological observation and viral load titer assay. The concentration and presence of the expressed IL12 was quantified and verified via ELISA assay. In summary, rAF-IL12 was proven to be safe, selectively replicating in chicken and cancer cells and was able to maintain its stability throughout several passages; thus enhancing its potential as an anti-breast cancer vaccine.
Highlights
The development of recombinant NDV has been primarily focused on increasing the oncolytic activity and therapeutic effect
Successful insertion of IL12 gene into the NDV genome was done by cloning the gene between two Nhe[1] restriction sites that were introduced between the M and F genes
The size of M/F region without IL12 is 377 bp, while in the presence of IL12, the size increases to 2 kb[14]
Summary
The development of recombinant NDV has been primarily focused on increasing the oncolytic activity and therapeutic effect. We inserted a human IL12 gene into the NDV genome at the position between M and F genes. A study conducted by Sangro et al.[18] proved that an adenovirus encoding IL12 was able to target liver cancer cells through intratumoral injections. IL12 was able to induce anti-tumor effects while reducing systemic toxicity[18]. The objective of this study was to evaluate the safety, stability and cytotoxic effect of rAF-IL12 against human breast cancer cells in vitro and in vivo for the potential development of an efficacious anti-breast cancer vaccine
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