T Cells from Melanoma Lymph Nodes Show Promise for Adoptive Immunotherapy

T cells generated from tumor-draining lymph nodes of patients with stage III melanoma were shown to mediate protective immune responses in vivo in a melanoma xenograft model, according to a report published in the Journal of Immunotherapy.¹

In mice bearing human melanoma xenografts, adoptive transfer of the T cells showed dose-dependent improvement in survival.

Tumor-specific T cells were cultured and expanded from melanoma-draining regional lymph nodes in patients who had undergone lymph node dissection.

“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 Julian Kim, MD, Chief Medical Officer at University Hospitals Case Medical Center Seidman Cancer Center.²

In the study, T-cell priming occurs naturally in vivo by the progressively growing tumor in stage III patients, rather than ex vivo priming with antigen or in vivo vaccination. The T cells are naturally primed against defined and undefined tumor antigens, which may lead to a broader response to tumor antigens.

After a 14-day culture activation and expansion in the presence of IL-2, tumor draining lymph node cells contained about 60% CD4-activated and about 40% CD8-activated T cells. The immune cells showed activity against four known melanoma antigens, suggesting melanoma specificity in the T-cell population.

The combination of CD4+ and CD8+ T cells is advantageous because CD4+ cells produce cytokines that support CD8+ cells, which may eliminate the need for exogenous cytokines, particularly IL-2, and the associated toxicity.

“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 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.”

A new phase I clinical trial using the technique is underway at the UH Seidman Cancer Center for patients with advanced melanoma.

References:

• Zhang M, Graor H, Visioni A, et al. (2015). T Cells Derived From Human Melanoma Draining Lymph Nodes Mediate Melanoma-specific Antitumor Responses In Vitro and In Vivo in Human Melanoma Xenograft Model. Journal of immunotherapy, 38(6): 229-238.
• University Hospitals Case Medical Center. (2015). UH Seidman Cancer Center investigators develop activated T cell therapy for advanced melanoma.