novel cancer vaccine strategy blocks death of tumor-specific cytotoxic
cells called killer T cells (a type of white blood cells that kills
key point of the strategy is increasing the amount of time a cytokine
responsible for regulating killer T cells stays in the body.
novel vaccine also increased the T cells' ability to resist cancer immune
New study may be a step forward in the
development of cancer vaccines that can find and attack tumors in the human
body. The study from Georgia Cancer Center at Augusta University is published
in Cancer Immunology Research
. The study has developed a
novel cancer vaccine strategy that blocks the death of tumor-specific cytotoxic
cells called killer T cells.
Using the Body's Immune System
to Fight Cancer
The lead scientists Drs.
Esteban Celis and Hussein Sultan state that the key to the novel cancer fighting vaccine
the amount of time a certain cytokine stays in the body.
The vaccine strategy works on
the premise of increasing the duration for which a cytokine known as
interleukin (IL2) stays in the body. The molecule IL2 is released by the immune
system that regulates the activity of killer T cells.
‘A novel cancer vaccine strategy is based on increasing the amount of time a cytokine (cell-signaling molecule that helps cell to cell communication) called IL2 stays in the body.’
"After administering peptide-based
vaccines in mouse models of cancer, we saw that sustained IL2 signaling dramatically
increased the number of tumor-specific cancer-killing T cells (CD8+),"
said Dr. Hussein Sultan, a postdoctoral fellow in the laboratory of Celis,
leader of the Center's Cancer Immunology, Inflammation and Tolerance Program.
Moreover, the peptide-based vaccines
increased the ability of the T cells to resist cancer immune evasion that was
made possible by a protein known as programmed death-ligand 1 (PD-L1).
PD-L1 is a protein that is produced by tumor
cells which allows them to evade destruction by the killer T cells.
The two findings show that peptide-based
vaccines substantially improved the anti-tumor efficacy in tumor-bearing mice.
Interleukin 2: The secret
"In order to be effective, IL2 needed to
be administered either as a complex of IL2 and anti-IL2 antibody, or in the
form of polyethylene glycol-modified IL2 (PEG-IL-2). These formulations
prolonged the half-life of IL2, allowing sustained activation of the IL2
receptor on vaccine-generated T cells, allowing them to survive longer in the
body and attack the tumor." Celis said.
Why Cancer Vaccine Efficacy
Cancer cells are created when our normal
cells undergo a mutation. This means that cancer cells are most often than not
similar to healthy cells. The fact that most tumor antigens
not foreign proteins makes it difficult for vaccines to induce antibodies
against tumors. Moreover, T cells are trained to only recognize and destroy
The team hopes that the study findings will
help them find their way into clinical studies with human cancer patients.
- Hussein Sultan, Takumi Kumai, Valentyna I. Fesenkova, Aaron E. Fan, Juan Wu, Hyun-Il Cho, Hiroya Kobayashi, Yasuaki Harabuchi, Esteban Celis. "Sustained Persistence of IL2 Signaling Enhances the Antitumor Effect of Peptide Vaccines through T-cell Expansion and Preventing PD-1 Inhibition". Cancer Immunology Research, (2018); 6 (5): 617 DOI: 10.1158/2326-6066.CIR-17-0549