New Antibody Targets Aggressive Cancers
Researchers at the University of Queensland's Frazer Institute have developed an antibody designed to target triple-negative breast cancer and other aggressive cancer types. The antibody functions by assisting natural killer (NK) cells in identifying and eliminating cancer cells more effectively, while potentially reducing treatment roadblocks. This work was recently published in Molecular Therapy.
Associate Professor Fernando Guimaraes, a group leader at the Translational Research Institute within the Frazer Institute, stated that the developed antibody recognizes a unique part of the ROR1 protein. This protein is commonly found on aggressive cancer cells but is rarely present on healthy cells. The antibody aims to precisely target cancer cells, enhancing the immune system's ability to kill cancer while sparing healthy tissue.
Natural Killer Cell Enhancement
Natural killer cells are immune cells that survey the body, identifying and eliminating potentially cancerous or virus-infected cells. The research focuses on manipulating NK cells to improve their killing capabilities and direct them more efficiently towards specific diseases. This tailored approach enables NK cells to target cancers they might not naturally "see" due to cancer cell alterations.
This research represents a multi-disciplinary and translational collaboration involving several Australian and international organizations.
Mechanisms and Target Cancers
Cancer cells can adapt to suppress the immune response against them. The researchers identified two approaches to counter this: empowering NK cells to kill cancer cells and shielding NK cells from cancer signals that inhibit their activity.
The new antibody flags cancer cells that express the oncofetal receptor ROR1. This receptor is typically expressed during fetal development and is absent in adult tissues. However, cancer cells can re-express this receptor due to mutations, making it a viable target for NK cell-based therapies.
While the research is currently preclinical, it holds potential for future clinical applications. The team has specifically investigated the antibody's effectiveness against triple-negative breast cancer, a particularly challenging breast cancer subtype due to a lack of defined therapeutic targets. The expression of ROR1 on triple-negative breast cancer models provides a rationale for this targeting approach. Other cancers, such as ovarian cancers and some blood cancers, may also benefit from this approach.
Potential for Gentler Treatment
NK cell-based immunotherapy, especially when involving engineered NK cells expressing chimeric antigen receptors (CARs), offers a potentially gentler treatment option compared to CAR-T cell therapies. While CAR-T cells are effective for blood cancers, they can carry risks such as graft-versus-host disease (GvHD), cytokine release syndrome (CRS), and neurotoxicity.
Early-stage clinical trials indicate that NK cell-based immunotherapies generally exhibit fewer major toxicity issues, with GvHD rarely observed in donor-to-patient NK cell transfers and reduced instances of cytokine release syndrome. This suggests a more controlled and potentially less toxic treatment approach.
Future Directions
Further research is required to establish a comprehensive safety profile for the antibody. While existing evidence suggests lower toxicity for NK cell-based immunotherapy, more data is needed to confirm these conclusions. Additionally, defining the manufacturing pipeline for these antibodies and CARs is a critical next step.
Funding is essential to advance this research from its preclinical stage to potential clinical options. The researchers are engaged in discussions with translational industries regarding potential partnerships to move the development forward. The work is inspired by past immunotherapy successes, such as the development of the Gardasil vaccine, and aims to contribute to immunotherapy as a frontline cancer treatment.