Trojan-Horse Therapy Proves Effective against Several Cancer Tumor Types

Disguising tumor-fighting antibodies inside the molecules used by cancer to nourish tumor growth can help sneak by cancer’s defenses, offering a novel therapy approach. This "Trojan-horse" therapy has demonstrated effectiveness in laboratory settings against various cancer types, including hard-to-treat brain tumors that can be difficult to access due to the blood-brain barrier.

A study published on July 15 in ACS Central Science by the Yale School of Medicine (YSM, New Haven, CT, USA) highlights the therapy's success which is attributed largely to the strategically redesigned antibodies derived from lupus to target tumors while neutralizing their autoimmune effects. Termed “antinuclear antibodies,” these agents secretly attach to nucleic acid molecules absorbed by cancer cells from their surroundings for DNA synthesis and tumor growth. Upon reaching the tumor, these antibodies shed their disguise and release their potent antinuclear payloads, destroying the cancer cells.

Image: Lupus antibodies — represented by butterflies — float amidst a stream of nucleosides on their way into the nucleus of a live tumor cell (Photo courtesy of Yale School of Medicine)

In contrast to traditional methods that combine antibodies with chemotherapy to target specific tumor cell markers like HER2 or PD-L1, this therapy’s antibodies silently infiltrate the tumor environment. These antinuclear antibody-drug conjugates (ANADCs) locate tumors by tracking the DNA remnants near tumors, enabling them to find tumors that lack specific surface receptors and evade detection by conventional antibodies. The effectiveness of ANADCs has been validated in mouse models of breast and colon cancer, significantly extending survival in glioma mouse models. This targeted approach potentially reduces the harmful side effects often caused by less precise therapies that damage healthy tissues. Currently, efforts are focused on progressing this therapeutic strategy into clinical trials.

“By targeting extracellular nucleic acids instead of surface receptors, ANADCs can basically target any necrotic tumor regardless of type, making it a tumor-agnostic therapy” said James Hansen, MD, MS, senior author of the study, member of Yale Cancer Center, and radiation oncology chief of Yale’s Gamma Knife Program. “This technology gives us the opportunity to use antinuclear antibodies to deliver drugs, proteins, or gene therapies to tumors or other sites of damage associated with increased DNA release, such as heart attacks, strokes, or traumatic injuries,”

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