Published in Nature Communications the study states that researchers at VIB-UGent Medical Research Center worked on an immunotherapy that killed part of a tumor while awaking the immune system to attack surviving cancer cells through the use of mixed linage kinase domain like pseudokinase (MLKL) as an agent of cell necroptosis.
Xavier Saelens, principal investigator at VIB-UGent told us, “Recent work from other groups had suggested that tumor cells are susceptible to necroptosis and that necroptosis may lead to the release of cellular ‘Damage-Associated Molecular Patterns’ that make the dying cells immunogenic. We found a way to induce necroptosis in cancer cells in a controlled way.”
When cells die from necroptosis the immune system is alerted and begins to fight against cancer cells. “This phenomenon is also called immunogenic cell death, as the dying cells become examples for the immune system, which then learns and remembers which cells to search for and attack,” said Lien Van Hoecke one of the members on Saelens research team.
VIB-UGent stated that while chemo and radiotherapy can reduce tumor size, this form of treatment ultimately damages healthy cells. By using the human immune system as its own treatment, this has a benefit in reducing tumor size while maintaining healthy cells while confusing cancer cells.
Saelens said that this approach, of using MLKL as an ‘executioner’, had to led to the discovery that cellular immunity against neo-epitopes from cancer cells were induced by MLKL messenger Ribonucleic Acid (mRNA).
The treatment developed by Saelens and his team does not include a checkpoint inhibitor, which is generally standard for melanoma treatment according to Saelens. However, he said, “The outcome of the MLKL mRNA therapy that we discovered is further improved when combined with a checkpoint inhibitor. One may hope that in the clinic such a combination will improve the success rate of immune checkpoint inhibitors.”
