Washington: A research team has now discovered that an immune checkpoint molecule they developed for cancer immunotherapy, also protects against future development of multiple types of cancer when administered by itself.
The study, conducted at the University of Louisville, was published in the journal Cancer Research.
Earlier studies have shown that the recombinant protein molecule SA-4-1BBL enhances the therapeutic efficacy of cancer vaccines with success in pre-clinical animal models. It accomplishes this by boosting the effectiveness of CD8+ T cells, adaptive immune cells trained to target the tumour for destruction.
Surprisingly, when the researchers treated normal healthy mice with SA-4-1BBL alone, the mice were protected when the researchers later exposed them to different types of tumour cells.
Speaking about it, lead author Haval Shirwan said, “The novelty we are reporting is the ability of this molecule to generate an immune response that patrols the body for the presence of rare tumour cells and to eliminate cancer before it takes hold in the body.”
Shirwan added that generally, the immune system will need to be exposed to the tumour, recognise the tumour as dangerous, and then generate an adaptive and tumour-specific response to eliminate the tumour that it recognises.
Shirwan added that the finding is very surprising because the immune system has not seen a tumour, so the response is not to the presence of a tumour.
According to researchers, the molecule generates a tumour immune surveillance system through activation of what are known as CD4+ T cells and innate NK cells, thereby protecting the mice against various cancer types they have never had.
This function is an indication of the molecule’s effectiveness in cancer immunoprevention.
The study saw mice that had never had cancer being treated with SA-4-1BBL alone. They were then challenged with cervical and lung cancer tumour cells at various time intervals.
The mice showed significant protection against tumour development, with the greatest protection when challenged two weeks after treatment with SA-4-1BBL. The cancer immunoprevention effect generated by SA-4-1BBL lasted more than eight weeks.
Additional testing showed that CD8+ T cells were not required for the protection, but when CD4+ T and NK cells were eliminated in the mice, protection failed, indicating these two cell types were necessary to achieve the effect. The lack of necessity for CD8+ T cells indicates the process is not one of conventional acquired immunity.
“We are very excited about the cancer immunoprevention possibilities of this molecule. Its effectiveness is not tumour specific, and as a natural ligand, it does not cause toxicity, as is found with 4-1BB agonist antibodies. Plus, the fear of autoimmunity is highly minimised, as evident from our data, because it is activating the innate immune cells,” said co-author of the study Esma Yolcu.
Shirwan and Yolcu plan to conduct further tests for SA-4-1BBL in cancer immunoprevention.