A research team led by Professor Jun-O Jin of University of Ulsan College of Medicine at Asan Medical Center has developed a novel immunotherapeutic agent by inserting an immune adjuvant into tumors surgically removed from patients.

Activated dendritic cells directly attacked cancer cells, leading to a marked reduction in tumor size. The therapeutic effect was confirmed in an animal model.

▲ (From left) Professor Jun-O Jin and researcher So-Jung Kim of the Department of Microbiology at the University of Ulsan College of Medicine and Asan Medical Center

Although advances in cancer therapeutics have steadily improved cure rates, metastatic cancer that has spread to other organs remains associated with poor survival. Frequent phenotypic alterations limit available treatment options and reduce therapeutic efficacy. In response to these challenges, there has been a growing need for a novel strategy that can target metastatic lesions in a patient-tailored manner while being less affected by tumor heterogeneity.

Professor Jun-O Jin and researcher So-Jung Kim of the Department of Microbiology at the University of Ulsan College of Medicine and Asan Medical Center recently announced the development of Immunogenic Apoptotic Bodies, or iABs. The team generated apoptotic bodies from surgically resected tumor tissues and inserted an immune adjuvant into them, enabling effective targeting of residual metastatic cancer cells remaining in the body.

The findings were recently published in ‘Cancer Communications’ (impact factor 24.9), a leading international journal in the fields of cancer research and oncology.

Immunotherapy is a treatment modality that enables dendritic cells, a key component of the immune system, to recognize cancer antigens and selectively eliminate tumor cells. Dendritic cells play a pivotal role in initiating immune responses by presenting tumor antigens to other immune cells.

However, in metastatic cancer, sufficient immune activation is often not achieved, resulting in treatment failure. In addition, adverse events such as immune-related reactions have been reported, underscoring the need for the development of novel immunotherapeutic strategies.

Recently, therapeutic strategies that induce apoptosis through immune cells have drawn increasing attention. Apoptotic bodies generated during the death of cancer cells contain abundant tumor-derived antigens and have therefore been investigated as potential agents for tumor-targeted therapy. However, conventional apoptotic bodies have faced limitations, including difficulty in delivering them selectively to specific immune cells and the potential to induce immunosuppressive responses.

To overcome these challenges, Professor Jun-O Jin’s research team extracted cancer-derived apoptotic bodies from surgically resected primary tumors and incorporated monophosphoryl lipid A (MPLA), an immune adjuvant known to promote dendritic cell activation, into the particles to develop iABs. This strategy was designed to enhance antitumor immune responses while minimizing the risk of immune suppression.

To recapitulate clinical conditions similar to those of patients with metastatic or residual disease, the researchers established mouse models bearing two tumors per animal by implanting highly metastatic breast cancer, colorectal cancer, and melanoma cells. One tumor was surgically removed, and iABs were generated from the resected tissue. After a defined interval, the iABs were administered to target the remaining tumor on the contralateral side, and therapeutic efficacy was evaluated.

The results demonstrated that administration of iABs induced antigen-specific T cell activation initiated by dendritic cells, leading to a selective immune-mediated attack on the residual tumor. Across all metastatic models, including breast cancer, colorectal cancer, and melanoma, the remaining tumors showed a marked reduction in size and suppressed growth. In some models, complete remission, defined as the total disappearance of detectable tumor, was observed.

To elucidate the underlying therapeutic mechanism, the team analyzed immune cell responses. Cytotoxic T lymphocytes isolated from iAB-treated mouse models were found to recognize tumor antigens in an antigen-specific manner and rapidly eliminate target tumor cells within a short period of time. Notably, no significant adverse effects, such as hepatotoxicity or systemic inflammatory responses, were observed.

Professor Jun-O Jin of the Department of Microbiology at the University of Ulsan College of Medicine and Asan Medical Center stated “This study is meaningful in that it demonstrates the development of a highly immunocompatible therapeutic agent by utilizing surgically resected tumors as a treatment resource. Given the consistent therapeutic efficacy observed across different metastatic models, including breast cancer, colorectal cancer, and melanoma, we anticipate that these findings will provide an important foundation for the research and development of immunotherapies for metastatic cancer.”

This research was supported by the Basic Research Laboratory Program of the University of Ulsan College of Medicine and the Nano and Materials Technology Development Program.