A team from the University of Granada demonstrated the ability of LdrB bacterial toxin to kill cancer cells of the colon, cervix and breast, through gene therapy. Although the antitumor capacity of this component has not yet been tested in people, the proof of concept shows a promising technique for its subsequent application in humans.
Suicidal gene therapy consists of inducing at the cellular level specific genes that are not part of the organism or are defective, with the aim of killing certain harmful cells and thus combating certain diseases. This is the system that has been used by a team at the University of Granada (UGR) to stop the proliferation of several tumor cells (colorectal, cervical and breast) both in vitro and in vivo to stop the growth of cancer.
The technique is based on LdrB, a bacterial toxin that had not been studied in humans. The gene that encodes this toxin is transferred to the tumor cells through a molecular vehicle based on Tet-ON 3G technology, and an antibiotic (doxycycline) which is used as an induction element for gene expression.
As team leader Houria Boulaiz Tassi explains, “doxycycline allows us to control gene expression and analyze its effect.” The system, based on the LdrB toxin , has been patented and described in the journal Cancers.
By acting inside the tumor cells, the LdrB toxin stops the cell cycle and induces cell death with the formation of pores in the tumor cells. Another advantage of the system is that it expresses fluorescence, which allows the tumor cells to be traced in case of metastasis . This also gives it a therapeutic function, another diagnosis, which makes it promising for its subsequent application in humans.
Together, the new system patented by the researchers is a proof of concept of the potent antitumor capacity of the LdrB toxin as a system of gene therapy against cancer, both in vitro and in vivo.
Currently, researchers are working to specifically target this new therapeutic tool towards tumor cells in general and cancer stem cells, in particular through specific tissue promoters to increase their efficacy and biosecurity.
Results without side effects
LdrB toxin drastically reduced the proliferation of colorectal cancer tumors in vivo similar to that produced by the main chemotherapy drugs used such as Fluorouracil or FOLFOX, but without causing any side effects, unlike that produced by conventional chemotherapy that has been shown to have multiple side effects, such as nausea, hair loss and even infertility.
Currently, there are other toxins that are being used in clinical trials for different types of cancer, such as botulinum toxin or diphtheria A. In comparison, the great advantage of the LdrB toxin is its small size (only 35 amino acids), facilitating its supply.