Novel Adoptive Immunotherapy Based on T Cells for Advanced Melanoma

Novel Adoptive Immunotherapy Based on T Cells for Advanced Melanoma

A recent study led by researchers at the University Hospitals Case Medical Center Seidman Cancer Center reported a new promising therapeutic strategy based on adoptive immunotherapy for advanced melanoma. The study was published in the Journal of Immunotherapy and is entitled “T Cells Derived From Human Melanoma Draining Lymph Nodes Mediate Melanoma-specific Antitumor Responses In Vitro and In Vivo in Human Melanoma Xenograft Model”.

Melanoma is the most dangerous form of skin cancer, and is caused by damage to skin cells (usually by ultraviolet radiation from sunshine or tanning beds), which triggers mutations that are not repaired allowing cells to rapidly multiply and generate malignant tumors.

It has been previously shown in mice with malignant tumors that lymph nodes contain antigen-specific T cells (important immune cells) that are capable of mediating a protective immune response upon adoptive transfer. The presence of these naturally occurring tumor-draining lymph nodes in humans requires, however, further investigation.

Researchers have now developed a strategy in which the lymph nodes of patients with growing melanoma are surgically removed and the immune cells extracted, so that the expansion and activation process of the crucial T cells can be tightly regulated in a laboratory setting. These activated T cells are then transferred back into the patient through intravenous administration in order to stimulate the patient’s immune system to attack the malignant cells. The procedure allows the generation of a large number of activated T cells. This novel strategy for cancer treatment is known as adoptive immunotherapy, and it is only available at a few institutions worldwide.

“This study is unique in that the source of T cells for therapy is derived from the lymph node, which is the natural site of the immune response against pathogens as well as cancer,” explained the study’s senior author Dr. Julian Kim in a news release. “These encouraging results provide the rationale to start testing the transfer of activated T cells in a human clinical trial.”

The team found that the activated T cells generated through their novel technique were reactive against different melanoma antigens, leading to cancer cell death in vitro in cell cultures and an improved survival when tested in vivo using a human melanoma xenograft model.

Based on these promising results, a new Phase I human clinical trial in patients with advanced melanoma has been recently launched to test this adoptive immunotherapy strategy.

This study showed for the first time that natural lymph node T cells from patients with advanced melanoma can be readily cultured and expanded in laboratory, being able to trigger a protective immune response against the tumor both in vitro and in vivo.

“The infusion of activated T cells has demonstrated promising results and is an area of great potential for the treatment of patients with cancer,” concluded Dr. Kim. “We are really excited that our method of activating and expanding T cells is practical and may be ideal for widespread use. Our goal is to eventually combine these T cells with other immune therapies which will result in cures. These types of clinical trials place the UH Seidman Cancer Center at the forefront of immune therapy of cancer.”

The team is also testing this T cell approach in patients with pancreatic cancer, and hopes to extend their research to other types of cancers including breast, lung and colorectal.

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