New method enhances the efficacy of bispecific antibody therapies in treating solid tumors

Professor Seung-Woo Lee and PhD candidate Kun-Joo Lee from the Department of Life Sciences at Pohang University of Science and Technology (POSTECH), in collaboration with NeoImmuneTech Director Donghoon Choi and Professors Dae Hee Kim and Sun Shim Choi from Kangwon National University, have revealed a groundbreaking method to significantly enhance the efficacy of bispecific antibody therapies in treating solid tumors. Their findings were published on May 13 in "Cell Reports Medicine", an international journal of healthcare research.

Bispecific antibodies, which can simultaneously bind to two different antigens, are currently under active investigation in cancer therapy research. Bispecific T cell engagers can engage both T cells and tumor cells at the same time, prompting T cells to effectively attack the tumors. Over the past two years, the FDA has approved 7 bispecific T cell engagers, establishing this approach as a leading strategy in the antitumor immunotherapy market. Despite their success in treating blood cancers, bispecific T cell engagers have been less effective against solid tumors such as lung and colon cancers. This limitation arises because many solid tumors have a low number of T cells needed for tumor eradication, and the existing T cells are often exhausted in terms of functionality.

To overcome these challenges, the research team utilized rhIL-7-hyFc1) (NT-I7, epinepatakin-alfa), a recombinant protein currently undergoing clinical trials at NeoImmuneTech. This protein is known to increase the number of T cells, and the research team used it in animal studies. The results demonstrated that in animal models of colon and skin cancer, rhIL-7-hyFc significantly boosted the number of "bystander T cells" within solid tumors. Although bystander T cells are not naturally tumor-specific, but when activated, they can respond to and kill tumor cells. The study found that the increased bystander T cells in solid tumors, induced by rhIL-7-hyFc, could indeed be activated by bispecific antibodies to destroy tumor cells. This breakthrough indicates that rhIL-7-hyFc can overcome the limitations of bispecific antibodies in treating solid tumors by addressing the issues of insufficient T cell numbers and functionality.

POSTECH Professor Seung-Woo Lee, who led the research, stated, "We have identified the potential of rhIL-7-hyFc as a catalyst to improve the antitumor efficacy of bispecific T cell engagers." He highlighted the significance of the research, adding, "We hope that our findings will be validated in clinical trials, which would greatly benefit the currently stagnant field of immunotherapy in solid tumors."

The research was conducted with support from the Korea Drug Development Fund and the National Research Foundation of Korea.

Source:
Journal reference:

Lee, K.-J., et al. (2024). IL-7-primed bystander CD8 tumor-infiltrating lymphocytes optimize the antitumor efficacy of T cell engager immunotherapy. Cell Reports Medicine. doi.org/10.1016/j.xcrm.2024.101567.

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