Related Experiment Video
Updated: Oct 16, 2026
Generation of Induced Pluripotent Stem Cells from Human Melanoma Tumor-infiltrating Lymphocytes
Published on: November 11, 2016
Immunogenetic therapy of human melanoma utilizing autologous tumor cells transduced to secrete granulocyte-macrophage
1Division of Surgical Oncology, University of Michigan, Ann Arbor 48109, USA.
Abstract:
We performed a clinical study of five patients with melanoma to evaluate the immunobiological effects of retrovirally transduced autologous tumor cells given as a vaccine to prime draining lymph nodes. Patients were inoculated with both wild-type (WT) and GM-CSF gene-transduced tumor cells in different extremities. Approximately 7 days later, vaccine-primed lymph nodes (VPLNs) were removed. There was an increased infiltration of dendritic cells (DCs) in the GM-CSF-secreting vaccine sites compared with the WT vaccine sites. This resulted in a greater number of cells harvested from the GM-CSF-VPLNs compared with the WT-VPLNs at a time when serum levels of GM-CSF were not detectable. Four of five patients proceeded to have the adoptive transfer of GM-CSF-VPLN cells secondarily activated and expanded ex vivo with anti-CD3 MAb and IL-2. One patient had a durable complete remission of metastatic tumor. Utilizing cytokine (IFN-gamma, GM-CSF, IL-10) release assays, GM-CSF-VPLN T cells manifested diverse responses when exposed to tumor antigen in vitro. In two of two patients, GM-CSF-VPLN T cell responses were different from those of matched WT-VPLN cells. This study documents measurable immunobiologic differences of GM-CSF-transduced tumor cells given as a vaccine compared with WT tumor cells. The complete tumor remission in one patient provides a rationale to pursue this approach further.
Insights
This study shows that a melanoma vaccine using GM-CSF gene-transduced tumor cells increases dendritic cell infiltration and T cell responses in lymph nodes. One patient achieved a complete remission of metastatic melanoma.
Area of Science:
- Oncology
- Immunology
- Gene Therapy
Background:
- Melanoma is a significant public health concern.
- Current treatments for metastatic melanoma have limitations.
- Autologous tumor cell vaccines are being explored as a therapeutic strategy.
Purpose of the Study:
- To evaluate the immunobiological effects of retrovirally transduced autologous tumor cells as a vaccine.
- To compare the effects of wild-type (WT) tumor cells versus granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-transduced tumor cells.
- To assess the potential for adoptive transfer of vaccine-primed lymph node cells.
Main Methods:
- A clinical study involving five melanoma patients.
- Inoculation with both WT and GM-CSF gene-transduced autologous tumor cells in different extremities.
- Surgical removal of vaccine-primed lymph nodes (VPLNs) approximately 7 days post-inoculation.
- Ex vivo activation and expansion of GM-CSF-VPLN cells with anti-CD3 MAb and IL-2 for adoptive transfer.
- Cytokine release assays to assess T cell responses to tumor antigen.
Main Results:
- Increased infiltration of dendritic cells (DCs) at GM-CSF-secreting vaccine sites compared to WT sites.
- Greater number of cells harvested from GM-CSF-VPLNs compared to WT-VPLNs.
- One patient achieved a durable complete remission of metastatic tumor following adoptive transfer.
- GM-CSF-VPLN T cells showed diverse responses to tumor antigen in vitro, differing from WT-VPLN cells in some patients.
Conclusions:
- GM-CSF gene-transduced tumor cell vaccines induce measurable immunobiological differences compared to WT tumor cells.
- The observed increase in DCs and distinct T cell responses suggest enhanced anti-tumor immunity.
- The complete tumor remission in one patient supports further investigation of this therapeutic approach.
