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Published on: January 3, 2013
[Anti-pancreatic cancer immune response induced by K-ras mutated peptide]
Yang He1, Bo Yang, Chang-Geng Ruan
1Jiangsu Provincial Institute of Hematology, The First Affiliated Hospital, Suzhou University, Suzhou, Jiangsu, 215006, P.R.China. heyang1963@163.com
Background & Objective:
Since most tumor antigens are uncertain, the immunotherapy against tumors still lingers in clinical trials. Because k-ras proto-oncogene specifically expresses in pancreatic cancer cells with constant mutation site, it may be an ideal target for immunotherapy against pancreatic cancer. This study was to evaluate the feasibility of inducing immunotherapy on pancreatic cancer by K-ras mutated peptides, give experimental evidence to clinical individual therapy on pancreatic cancer.
Methods:
k-ras oncogene was amplified by reverse transcription-polymerase chain reaction (RT-PCR)u its mutation type was detected by flow cytometry. T cells were induced by dendritic cells, which had been pulsed with synthesized mutated peptide. Killing effect of tumor specific T cells on pancreatic cancer cell line Patu8988 was assessed by MTT assay.
Results:
There was a point mutation (GGT-->GTT) in the 12th codon in Patu8988 cellu the amino acid was mutated to valine. The mutation epitope was efficiently presented on dendritic cells'surface. The cytotoxic T cells induced by mutated peptide could kill Patu8988 cells efficiently.
Conclusions:
The mutated peptide can efficiently induce immunocytes to kill pancreatic cancer cells, which have k-ras mutation site. This finding provides experimental clue for immunotherapy against pancreatic cancer.
Insights
Immunotherapy targeting mutated k-ras peptides shows promise for pancreatic cancer treatment. This approach effectively induces immune cells to eliminate cancer cells with specific k-ras mutations.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Current cancer immunotherapies face challenges due to uncertain tumor antigens.
- The k-ras proto-oncogene, with its specific mutation site in pancreatic cancer, presents a potential therapeutic target.
Purpose of the Study:
- To assess the feasibility of inducing immunotherapy against pancreatic cancer using k-ras mutated peptides.
- To provide experimental evidence for personalized immunotherapy in pancreatic cancer treatment.
Main Methods:
- K-ras oncogene mutations were identified using reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry.
- Dendritic cells pulsed with synthesized mutated peptides were used to induce T cells.
- The efficacy of tumor-specific T cells in eliminating the pancreatic cancer cell line Patu8988 was evaluated via MTT assay.
Main Results:
- A specific point mutation (GGT to GTT) in the 12th codon of the k-ras gene was identified in the Patu8988 cell line, resulting in a valine amino acid change.
- The mutated epitope was effectively presented on dendritic cell surfaces.
- Induced cytotoxic T cells demonstrated efficient killing of Patu8988 cells.
Conclusions:
- Mutated k-ras peptides can effectively stimulate immune cells to target and eliminate pancreatic cancer cells harboring k-ras mutations.
- This study offers a potential experimental strategy for developing immunotherapies against pancreatic cancer.
