Attaching ‘fake targets’ to tumor cells enables antigen-independent immunotherapy

A research team has introduced a novel cancer immunotherapy strategy. This approach involves attaching “fake targets” to tumor cells to guide immune cell attacks, overcoming the limitations of conventional antibody-based therapies. The study is published in ACS Nano.

The team was led by Professor Won Jong Kim from the Department of Chemistry and POSTECH–Catholic biomedical engineering institute at POSTECH, along with Ph.D. candidate Seonwoo Kang, and collaborated with Dr. Junseok Lee’s team at UCLA on this work.

One of the major challenges in cancer treatment is the ability of tumors to evade immune surveillance. Traditional antibody therapies rely on the recognition of specific antigens expressed on the tumor cell surface. However, antigen expression is often low or heterogeneous in real tumors. Some tumors even lack the specific antigen—so-called “antigen-negative tumors”—greatly limiting the therapeutic efficacy.

To address this, the research team developed a novel “universal antibody” (Univody) technology, enabling immune cells to attack tumors regardless of antigen presence. By genetically engineering a construct that allows the stable expression of antibody Fc fragments on the tumor surface, the researchers effectively marked tumor cells for immune recognition.

A specialized delivery system, termed LPP-PBA (lipopolyplex modified with phenylboronic acid), was designed to selectively deliver this genetic material. PBA moieties on the surface of LPPs specifically interact with overexpressed sialic acid residues on cancer cells, ensuring tumor-specific delivery and expression of the antibody fragments.

The engineered tumor cells expressing Fc fragments became immediate targets for immune attack. Experimental results confirmed that NK (natural killer) cells recognized the Fc-tagged tumor cells, launched cytotoxic responses, and triggered broader immune activation. In animal models of triple-negative breast cancer and melanoma, the Univody system significantly suppressed tumor growth.

Unlike conventional antibody therapies, the Univody platform does not rely on tumor-specific antigens, offering a universal and flexible immunotherapeutic approach.

“Because it functions independently of antigen type, this platform holds promise for broad application across various cancers,” said Professor Kim. Dr. Junseok Lee from UCLA emphasized the innovation of the strategy. “Directly tagging antibody fragments onto tumor cells represents a transformative approach that can overcome key limitations in current cancer immunotherapies.”