Researchers have developed a nanovaccine that, when combined with antibodies and ibrutinib, shows potential as an effective treatment for melanoma.
Immune checkpoint therapy, a form of cancer therapy which targets the immune system, has proven to be an effective treatment method for melanoma, the most aggressive type of skin cancer. However, immune checkpoint therapy is limited by a low response rate, severe side effects, and acquired resistance to treatment. There is a need to develop an alternative treatment option that can sensitize melanoma to immune checkpoints.
Researchers led by João Conniot, PhD, a postdoctoral fellow at Tel Aviv University in Israel, and Anna Scomparin, PhD, a research associate at the Satchi-Fainaro Lab at Tel Aviv University, have found a potential solution in a nanovaccine, a type of vaccine that uses nanoparticles as carriers to stimulate the immune system and trigger more effective immune responses. The investigators inserted peptides—short chains of amino acids—expressed in melanoma cells into nanoparticles to create nanovaccines. They combined each vaccine with an anti–programmed cell death protein 1 (anti–PD-1) antibody and an anti-OX40 antibody for immunosuppression blockade and effector T-cell stimulation, respectively. Additionally, each vaccine was combined with ibrutinib, a myeloid-derived suppressor cell inhibitor, before being injected into melanoma-bearing mice.
"The nanoparticles acted just like known vaccines for viral-borne diseases," comment the researchers, led by first author Ronit Satchi-Fainaro, PhD, head of the Laboratory for Cancer Research and Nanomedicine at Tel Aviv University, in the study now published in Nature Nanotechnology. "They stimulated the immune system of the mice, and the immune cells learned to identify and attack cells containing the two peptides—that is, the melanoma cells. This meant that, from now on, the immune system of the immunized mice will attack melanoma cells if and when they appear in the body."
In addition to their prophylactic effects, the nanovaccines also proved successful in treating primary tumors in the mice by delaying disease progression and increasing survival.
"Our research opens the door to a completely new approach—the vaccine approach—for effective treatment of melanoma, even in the most advanced stages of the disease," conclude Dr. Satchi-Fainaro and colleagues. "We believe that our platform may also be suitable for other types of cancer and that our work is a solid foundation for the development of other cancer nanovaccines."
For More Information
Conniot J, Scomparin A, Peres C, et al (2019). Immunization with mannosylated nanovaccines and inhibition of the immune-suppressing microenvironment sensitizes melanoma to immune checkpoint modulators. Nat Nanotechnol. [Epub ahead of print] DOI:10.1038/s41565-019-0512-0
Image credit: Victor Segura Ibarra and Rita Serda