An anti-FGFR1 humanized antibody drug candidate offers new approach to fight aggressive lung cancer

Researchers have introduced a new antibody-based treatment, OM-RCA-01, which shows great promise against lung cancer in experimental models. The therapy, developed by a team led by Dr. Ilya Tsimafeyeu at BUCARE in New York, with collaborators at Fox Chase Cancer Center, Altogen Labs, and other institutions, was recently featured in the ESMO journal Immuno-Oncology & Technology. The therapy is effective on its own and enhances the impact of existing immunotherapy drugs such as nivolumab and pembrolizumab. Immunotherapy drugs help the immune system recognize and attack cancer cells more effectively.

Fibroblast growth factor receptor 1 is the target protein of OM-RCA-01 and is known to help cancer cells grow and resist treatments that activate the immune system. This receptor acts like a switch that promotes tumor survival and spread, making it a key target for treatment. The scientists conducted a series of carefully designed experiments to study how antibodies affect cancer cell behavior, immune system function and reduce tumor growth. “Targeting fibroblast growth factor receptor 1 is both a challenge and an opportunity because it plays a key role in helping tumors survive and evade the immune system,” said Dr. Tsimafeyeu.

The results of this study are significant. OM-RCA-01 alone resulted in significant reductions in tumor size in experimental lung cancer models. These models involve growing human-like tumors in animals to study the effects of treatments. When paired with immunotherapy drugs that help activate the immune system, the antibodies significantly increase levels of proteins that signal immune activity. For example, when the two therapies were combined, tumor growth was almost completely halted in a short period of time, highlighting its potential to significantly improve current treatments.

Encouragingly, anti-FGFR1 antibodies were also found to be safe, even when used at higher doses than typically required. Safety studies show no harmful effects in animals at therapeutic levels and beyond. In a pivotal experiment, combining OM-RCA-01 with pembrolizumab resulted in significant tumor reduction compared with pembrolizumab alone. Pembrolizumab is a well-known immunotherapy that blocks a protein called programmed cell death protein 1, preventing the immune system from attacking cancer cells. Dr. Tsimafeyeu emphasized, “These findings highlight the potential of OM-RCA-01 to change the way we treat cancer by addressing treatment resistance.”

Further research showed that OM-RCA-01 not only directly affects cancer cells, but also counteracts barriers created by the environment surrounding the tumor. This environment, called the tumor microenvironment, includes a variety of cells and molecules that protect tumors from attack by the immune system. The antibody weakens these barriers, allowing immune cells to work more effectively. The dual ability to target cancer cells and their surrounding environment makes OM-RCA-01 a powerful tool in cancer treatment.

There is optimism about the therapy’s potential to enter human clinical trials. Clinical trials are studies involving volunteers testing new treatments. Plans are underway to test OM-RCA-01 in patients with lung cancer that expresses fibroblast growth factor receptor 1 and has not responded to standard treatments. Researchers believe the antibody could be a major advance in cancer treatment, bringing new hope to patients facing difficult-to-treat and aggressive diseases.

Journal reference

Tsimafeyeu I., Makhov P., Ovcharenko D., et al., “OM-RCA-01, a novel anti-FGFR1 monoclonal antibody, exhibits potent antitumor activity and enhances the efficacy of immune checkpoint inhibitors in lung cancer models. “Immunology technology. 2024 Jul 26;23:100725. DOI: https://doi.org/10.1016/j.iotech.2024.100725

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