ADC疗法封面图

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For many malignant hematologic diseases, stem cell transplantation remains the sole curative option. This treatment involves first using chemotherapy to eliminate the patient's own hematopoietic stem cells and most of their blood cells. Then, donor-derived stem cells are infused into the patient to replace the diseased blood system and rebuild a healthy one.

Despite being a well-established treatment method, as the brief description above suggests, the process is quite arduous for patients. Additionally, this complex therapy can pose various risks, such as infections and toxic damage to vital organs.

To improve hematopoietic stem cell transplantation, researchers at the University of Basel have recently developed a new antibody-drug conjugate (ADC) that can rebuild the patient's entire blood system in a "gentler" manner. The study's findings were recently published in Nature.

Antibody-drug conjugates (ADCs) are a cutting-edge therapeutic approach in cancer treatment, linking potent cytotoxic drugs to specific antibodies. This allows direct targeting of cancer cells, minimizing harm to healthy tissues. Recent advancements have focused on improving linker stability and drug potency, which enhances the efficacy and safety of ADCs. Studies have shown promising results in both hematologic malignancies and solid tumors. For instance, the approval of drugs like trastuzumab deruxtecan for breast cancer marks significant progress in ADC technology, offering new hope for patients with previously limited treatment options.

ADCs are a type of antibody medication that specifically targets antigens, combining the potent effects of traditional chemotherapy drugs. A new study has designed an ADC targeting CD45, which is widely expressed on hematopoietic cells. This ADC can identify various blood cells within the patient, including hematopoietic stem cells, without recognizing other body cells, thus depleting the diseased hematopoietic system in an antigen-specific manner.

To prevent the new hematopoietic stem cells and their derived blood cells from being attacked by the ADC, researchers utilized genetic engineering to modify donor stem cells. They introduced a minor change in the CD45 molecule, which allows it to retain its function while evading the CD45-targeting ADC.

Researchers liken this new system combining CD45-targeted ADCs with engineered hematopoietic stem cells to a "blood exchange mixing board." The DJ gradually lowers the volume of the first song while increasing the volume of the second song until the first song fades out completely, offering a gentler approach compared to the existing "song-switching" method.

This new system has shown promising results in preclinical studies, with the modified hematopoietic stem cells successfully evading the CD45-targeting ADC. By specifically targeting antigens and depleting the diseased hematopoietic system, this approach holds great potential for improving blood cell therapy and treating various hematopoietic disorders. Further research and clinical trials are needed to fully evaluate the effectiveness and safety of this innovative system.

ADC疗法文中插图20240529

Using a new ADC therapy to eradicate tumors in mice with implanted tumors

Credit: Nature (2024). DOI: 0.1038/s41586-024-07456-3

In their paper, the researchers presented the positive outcomes achieved using this new method on both acute myeloid leukemia animal models and human cells in vitro. The animals showed no significant signs of toxicity while eradicating malignant tumors.

The team aims to commence preliminary clinical trials after further testing and optimization. This innovative approach could offer a new treatment option for patients who are not suitable for chemotherapy prior to stem cell transplantation, noted Dr. Romina Matter-Marone, one of the authors.


References

  1. Garaudé, S., Marone, R., Lepore, R. et al. Selective haematological cancer eradication with preserved haematopoiesis. Nature (2024). https://doi.org/10.1038/s41586-024-07456-3

  2. Researchers develop new method to remove blood cells in leukemia patients while building new blood system. Retrieved May 23, 2024 from https://medicalxpress.com/news/2024-05-method-blood-cells-leukemia-patients.html