A vaccine targeting tumors that produce a certain protein and receptor responsible for communication between cells and the body’s immune system, could initiate the immune response to fight cancer. These findings, published in the February 27, 2014 online edition of the journal Gene Therapy, build on previously reported research and could lead to new treatments for cancer.
The study’s principal investigator John Morris, MD, clinical co-leader of the Molecular Therapeutics and Diagnosis Program for the Cincinnati Cancer Center and co-leader of the UC Cancer Institute’s Comprehensive Lung Cancer Program, professor in the division of hematology oncology at the UC College of Medicine and UC Health medical oncologist, explained that a number of antitumor vaccines have shown promise for causing immune responses against tumor antigens to improve patient outcomes.
[Our research] provides evidence needed to begin investigating a vaccine in human cancer clinical trials to determine whether genetically modified tumor cells producing IL-15 and IL-15R? may induce anti-cancer responses…
Interleukin-15
Cancer immunotherapy is designed to stimulate a immune response which leads to the rejection and destruction of cancer cells. “Recently, human Interleukin-15 or IL-15, a member of the four ?-helix bundle family of cytokines, has entered clinical trials for treatment of patients with melanoma, a type of skin cancer, and renal cancer. In this study, we examined the effectiveness of a vaccination targeting tumors that produced IL-15 and its cell surface receptor called IL-15R-alpha and examined their ability to up-regulate (or increase) immune responses to tumor antigens,” Morris said. “We showed that the presence of both IL-15 with its receptor IL-15R? increased the cell-surface production and secretion of IL-15, and in turn, stopped tumor cells from reproducing.” [2]
“IL-15 is a powerful pro-inflammatory protein that can enhance immune responses,” Morris noted. IL-15 is a cytokine that regulates and stimulates lymphocyte subsets resulting in antiviral and anti-tumor activities. It is mainly mediated in a cell-to-cell contact called IL-15 trans-presentation, which, in turn, is mediated by a cell which tethers IL-15 to its plasmatic membrane complexed to IL-15 receptor alpha (IL-15R?). This surface complexes interact with interleukin-2 or Il-2 receptor beta and gamma on the adjacent cell to elicit signaling. Unlike Il-2, IL-15 protects from activation-induced cell death and does not promote regulatory cells. This is the basis of its activity against transplanted tumors and its adjuvanticity, evaluated in terms of antigen-specific antibody titers induced after parenteral immunization, in tumor and viral vaccines. [3]
Breast and prostate cancer
Researchers used IL-15 to develop a whole tumor cell vaccine to target breast (TS/A) and prostate (TRAMP-C2) cancer cells in animal models; results showed that tumor cells stopped growing after the vaccine was introduced and that beneficial effects were enhanced further when IL-15R? was co-produced by the vaccine cells.
Morris explained that vaccination with modified tumor cells producing IL-15 and IL-15R? slowed tumor growth and led to increased survival for animal models. Furthermore, the cells that control the immune responses (CD8+ T-cells and NK cells) were elevated in these tumors, showing evidence of a true immune response. “Our findings suggest that genetically altering tumor cells to produce IL-15 and IL-15R? can cause and enhance immune responses to tumor antigens found in these tumor cells and can be used as a vaccine to target these antigens,” he noted.
“Additionally, this provides evidence needed to begin investigating a vaccine in human cancer clinical trials to determine whether genetically modified tumor cells producing IL-15 and IL-15R? may induce anti-cancer responses,” Morris concluded.
For more information:
[1] Morris JC, Ramlogan-Steel CA, Yu P, Black BA, Mannan P, et al.
Vaccination with tumor cells expressing IL-15 and IL-15R? inhibits murine breast and prostate cancer Gene Therapy February 27, 2014, doi:10.1038/gt.2014.10 [Article][PubMed]
[2] Steel JC1, Waldmann TA, Morris JC. Interleukin-15 biology and its therapeutic implications in cancer. Trends Pharmacol Sci. 2012 Jan;33(1):35-41. doi: 10.1016/j.tips.2011.09.004. [Article][PubMed]
[3] Fehniger TA, Cooper MA, Caligiuri MA.Interleukin-2 and interleukin-15: immunotherapy for cancer. Cytokine Growth Factor Rev. 2002 Apr;13(2):169-83. [Article][PubMed]
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