Expanding and Activating a Cancer Patient’s Own T-Cells to Treat Their Cancer

A research team from UH Seidman Cancer Center in Cleveland, Ohio have designed a protocol for culturing activated T-cells from melanoma patients in order to expand and use the patient’s own T-cells to fight their cancer. This research, which may lead to treatments that save lives someday, was published in the Journal of Immunotherapy and will hopefully lead to clinical trials.

T-cells are a type of white blood cell in our bodies. These cells are born in the bone marrow, and they play a central role in orchestrating the immune response against foreign entities that enter our bodies. There are several different types of T-cells; some of the help other cells get revved up to fight an infection, others attack and destroy virus-infected cells, some suppress inappropriate immune responses, and others do a host of other interesting, and in some cases, poorly understood things. One function of T-cells is to identify and attack cancer cells. The problem is that T-cells from our own bodies often have trouble identifying cancer cells as truly foreign entities and deserve the T-cells ire.

Patients who suffer from a deadly type of skin cancer known as melanoma have T-cells coursing through their blood vessels that can trigger a protective immune response against the disease, according to a new study out of University Hospitals Case Medical Center Seidman Cancer Center and Case Western Reserve University School of Medicine. This new study demonstrates that T-cells isolated from lymph nodes of patients with melanoma can be expanded in number and activated in a laboratory-based cell culture system. These laboratory-grown T-cells can then be intravenously administered back into these same patients to treat their cancer.

Julian Kim, MD, Chief Medical Officer at UH Seidman Cancer Center, led the research team that did this fascinating study. According to Dr. Kim., he and his colleagues developed a completely novel technique that allowed them to successfully generate large numbers of activated T-cells that could be reintroduced back into the same patient to stimulate their immune system to attack or destroy their cancer.

“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,” said Dr. Kim who also serves as a Professor of Surgery at Case Western Reserve University School of Medicine and the Charles Hubay Chair at UH Case Medical Center. “These encouraging results provide the rationale to start testing the transfer of activated T-cells in a human clinical trial.”

In the Kim laboratory at the School of Medicine, Kim and his team developed a new method to grow T-cells from cancer patients and then activate them in a two-week cell culture system. The extracted the immune cells from lymph nodes that were exposed to growing melanoma in the patient’s body. Instead of trying to activate these tumor-sensitized T-cells in the body, the lymph nodes were surgically removed in order to activate and grow the T-cells in a tightly regulated environment in the laboratory. This novel approach to cancer treatment, which is termed “adoptive immunotherapy,” is only offered at a few institutions worldwide.

After these T-cells from melanoma patients were expanded and activated by exposing the cells to bits of proteins known to be on the surfaces of the melanomas, they were sicced on melanoma cells in culture.  These activated T-cells dutifully and efficiently killed the melanoma cells.  Well that’s all fine and good in culture, but could the cells to this in a living organism?  Do answer this question, Kim and others transplanted human melanomas into special laboratory mice that could grow human tumor tissue effective and then gave these mice intravenous infusions of the activated T-cells. These tumor-infested mice typically died from these transplanted tumors, but the mice treated with the patient-specific, activated T-cells survived in a concentration-dependent fashion.  In order words, the more activated T-cells the mice were given, the longer they lived and the better their bodies were able to fight the transplanted tumors.

The promising findings of this study have led to the recent launch of a new Phase I human clinical trial at UH Seidman Cancer Center in patients with advanced melanoma. “The infusion of activated T-cells has demonstrated promising results and is an area of great potential for the treatment of patients with cancer,” said 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.”

Kim and his team have also been investigating the possibility of using lymph nodes from patients with pancreatic cancer to develop additional T-cell therapies. Kim and his coworker would like to expand their program to eventually study other tumor types including lung, colorectal and breast cancers.