Development of a Smart Conjugate That Targets Difficult Cancer Cells and Produces Reactive Oxygen Species

Professor Na Gun's Catholic University Team Confirms Antibody-Photosensitizer-Induced Cancer Cell Death in KRAS Mutant Pancreatic Cancer Mouse Model

Schematic Diagram of Cancer Targeted Therapy Strategy Using Developed Antibody-Photoresponsive Agent Conjugate

After the antibody-photoresponsive agent attaches to the receptor overexpressed on the surface of pancreatic cancer, photodynamic cancer cell death can be induced by light irradiation. The immunogenic factors released as cancer cells die cause the maturation of surrounding immune cells, activating immune activity in the cancer microenvironment. Additionally, immune complexes formed by the attachment of the antibody's Fab region to cancer antigens are successfully phagocytosed by nearby antigen-presenting cells, rapidly and effectively enhancing immune capability against cancer cells. Figure description and provided by Professor Na Geon, Catholic University.

[Asia Economy Reporter Kim Bong-su] As the market for therapeutics that combine antibodies, which act as navigation to locate cancer cells, with anticancer drugs grows, a study has emerged that replaces anticancer drugs with photosensitizers.

The National Research Foundation of Korea announced on the 21st that Professor Na Geon’s research team at Catholic University developed an antibody-photosensitizer conjugate targeting mutant pancreatic cancer cells to simultaneously activate immune responses and cell death processes caused by oxidative stress.

The conjugate combines a photosensitizer that generates reactive oxygen species causing stress to surrounding cells in response to light, with an antibody that binds to biomolecules on the surface of cancer cells. Photodynamic therapy using photosensitizers and antibody therapy using monoclonal antibodies have traditionally been used independently to treat cancer.

When the research team injected this conjugate into a pancreatic cancer mouse model and irradiated the tumor tissue with light, the tumor size was reduced fivefold compared to the control group. Immune cells important for anticancer immune therapy (dendritic cells, T cells, natural killer cells) increased on average sixfold compared to antibody monotherapy and about twofold compared to photodynamic monotherapy, enhancing immune activity.

Antibodies used for metastatic pancreatic cancer work by binding to receptors on the cancer cell surface (epidermal growth factor receptor), recognizing cancer cells and blocking growth signal transmission within the cancer cells. However, in cancer cells with mutant genes (specific base mutations in the KRAS gene) found in 95% of pancreatic cancer patients, these antibodies can locate cancer cells but cannot block cancer cell growth signals. Therefore, in typical antibody-anticancer drug conjugates, the anticancer drug is released from the antibody to exert its anticancer effect.

The antibody-photosensitizer conjugate developed by the research team integrates both targeting and attacking functions into one, like existing antibody-anticancer drug conjugates, but simplifies factors that could affect successful attacks.

It can act on the cancer cell surface without entering the cancer cell, and without the need for the photosensitizer to separate from the antibody, cancer cells can be attacked on the surface simply by light irradiation. Existing conjugates must first enter the cancer cell, and after entry, the drug must properly separate from the antibody for the drug to attack the cancer cell.

The research team stated, “This will be a clue to antibody-conjugated photodynamic therapy for KRAS mutant pancreatic cancer cells,” adding, “This study is currently at the stage of verifying efficacy through preclinical trials, and we plan to promote product development that can be applied clinically through technology transfer or startup ventures in the future.”

The study results were published on the 16th of last month in the international journal Small.

This content was produced with the assistance of AI translation services.