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Tumor Cell–Loaded Dendritic Cells Improve Adoptive T-Cell Therapy

Dec 19, 2016 12:00:00 AM / by Stacy Matthews Branch, DVM, PhD

The use of tumor antigen–loaded dendritic cells leads to the expansion of CD4+ T helper & CD8+ cytotoxic T cells sufficient for prostate cancer treatment.Tumor-specific cytotoxic T cells are used in patients with cancer with the goal of providing specific recognition and destruction of tumor cells. In adoptive T cell therapy, tumor-specific T cells are collected and multiplied (expanded) outside the body. This is done to obtain a much larger number of the tumor-specific T cells that the patient can be treated with more successfully.

Prostate cancer remains a challenge to treat and is a common cause of death in men of advanced age. When detected early, it can be effectively treated initially by conventional means (surgery or radiation therapy). However, many patients still eventually succumb to metastasis. Personalized medicine is offering opportunities to develop approaches to treat cancer in ways that can be more effective and with fewer side effects. One approach is the use of adoptive T cell (ATC) therapy.

Recent research to enhance current ATC therapy approaches has yielded promising results. The researchers modified current ATC methods by using pre-treated dendritic cells (antigen-presenting cells). Dendritic cells loaded with prostate tumor antigen (i.e., incubated with experimental prostate cancer cells) were used to prime T cells collected from peripheral blood mononuclear cells of healthy volunteers. This led to the production of tumor-specific T cells.

The use of tumor antigen–loaded dendritic cells led to the expansion of CD4+ T helper and CD8+ cytotoxic T cells sufficient for patient treatment. Also observed was an increase in cytokine release (IFN-gamma) from these T cells. The cytotoxicity of the expanded T cells was stronger than those produced by incubation with ovarian cancer cells (controls).

The results from the study suggest that combining ACT with dendritic cell loading can produce sufficient numbers of T cell effectors that can target and destroy tumor cells. However, animal and clinical studies would be valuable to determine treatment safety and effectiveness. In addition, this modified ATC approach can be applied to other cancer types.

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Reference:
Vavrova K, et al. "Generation Of T Cell Effectors Using Tumor Cell-Loaded Dendritic Cells For Adoptive T Cell Therapy. - Pubmed - NCBI". Ncbi.nlm.nih.gov. N.p., 2016. Web. 28 Nov. 2016.

Topics: Cancer, Dendritic Cells, Vaccine Research, Basic Research

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