Radiation therapy, traditionally viewed as a localized cancer treatment, is increasingly recognized for its potential to stimulate systemic anti-tumor immune responses, especially when combined with other therapies. Recent research presented at the 2024 American Society for Radiation Oncology (ASTRO) Annual Meeting highlights a novel antibody-drug conjugate (ADC) that enhances radiation's immunogenic effects, offering a new pathway for immunotherapy-driven cancer treatment.
Radiation Therapy and Immune Modulation
Wen Jiang, M.D., Ph.D., notes that radiation therapy can modulate immune response, enhancing the immunogenicity of tumors and allowing the immune system to better recognize tumor cells. High doses of radiation can trigger immune signaling, driving a systemic anti-tumor response. This approach has been studied in several cancer types, including lung cancer, where stereotactic body radiation therapy is combined with immunotherapy.
Benjamin Schrank, M.D., Ph.D., explains, "We're moving beyond this notion of radiation as a local therapy to the idea that radiation can cause an immune response that then can synergize with other kinds of drugs to treat cancer."
Novel Antibody-Drug Conjugate (ADC) Mechanism
Schrank's recent research focuses on a first-in-class ADC designed to complement radiation therapy by stimulating an immune response. This ADC targets CD47, a protein used by tumors to evade the immune system. By binding to CD47, the drug facilitates the engulfment of cancer cells by immune cells, activating them in the process. Unlike traditional ADCs, this novel ADC does not deliver a chemotherapy drug, thus avoiding associated side effects.
The ADC activates immune cells using a bacterial toxin that stimulates the release of tumor DNA and other tumor cell components, which help train the immune system to recognize the cancer. This process aims to trigger an adaptive immune response, leading to the elimination of the tumor.
Future Directions in ADC Design
Jiang and Schrank envision this novel ADC as a potential game-changer in how ADCs are designed to treat cancer. "I hope this opens a new avenue of research that expands ADCs from just being focused on destroying tumor cells. A live tumor cell can be a great opportunity to train the immune system," Jiang says.
Schrank adds, "We're not just looking to kill cancer cells. We want to train the immune system to recognize tumors so it can continue fighting the cancer even after treatment."
