From Autoimmunity to Oncology: How a Lupus-Derived Antibody Could Help Fight Cancer

Related publication:

A lupus-derived autoantibody that binds to intracellular RNA activates cGAS-mediated tumor immunity and can deliver RNA into cells
https://www.science.org/doi/10.1126/scisignal.adk3320

In a groundbreaking study titled “A lupus-derived autoantibody that binds to intracellular RNA activates cGAS-mediated tumor immunity and can deliver RNA into cells,” researchers have identified a novel way to weaponize the immune system against cancer — using a molecule that originally plays a role in the autoimmune disease lupus.

The antibody, known as 4H2, was isolated from patients with systemic lupus erythematosus (SLE), an autoimmune condition characterized by chronic inflammation and overactivation of immune responses. While lupus is usually associated with the immune system attacking healthy tissue, the very mechanisms that make lupus dangerous may also hold the key to unlocking new cancer therapies.

🔬 Harnessing a Lupus Antibody to Activate Tumor Immunity

Chen et al., the authors of the study, discovered that 4H2 can enter cells and bind to RNA — a function not typically seen in antibodies. Once inside the cell, 4H2 forms complexes with endogenous RNA that activate a powerful immune sensor called cGAS (cyclic GMP-AMP synthase). This triggers a cascade of immune signals, particularly the production of interferons and inflammatory cytokines — natural immune responses that can be lethal to cancer cells.

What’s especially compelling is that this immune activation is selectively toxic to tumor cells such as those from the brain (glioblastoma), lung, and breast — but spares healthy cells like normal breast epithelial tissue. In mouse models, 4H2 even improved survival and enhanced the effects of immune checkpoint inhibitors, which are already used in modern cancer therapies.

🧠 How Does cGAS Work? A Cellular Alarm System

cGAS is a protein inside cells that acts like a security alarm. It normally detects foreign or misplaced DNA in the cytoplasm — such as viral DNA or DNA from dying tumor cells. Once it detects this DNA, cGAS creates a signal molecule called cGAMP, which activates another protein called STING to launch an immune response.

This response includes the production of type I interferons, which are known to help the immune system attack cancer cells. Though cGAS typically responds to DNA, in this study, it was activated indirectly via RNA delivered and bound by 4H2 — a twist that scientists are still unraveling but offers exciting therapeutic potential.

🔁 Lupus and Cancer: Reversing the Immune Overdrive

People with lupus often suffer because their immune systems mistake self-molecules like DNA or RNA as foreign, triggering chronic inflammation. This involves high levels of interferons and cytokines, especially those driven by cGAS and related pathways.

In lupus, this overdrive is harmful. But researchers are flipping the script — using the same immune tools to attack cancer cells, which are abnormal and often evade detection.

✅ Lupus involves interferon overactivation.
✅ These same signals are beneficial when aimed at tumors.
🔄 The 4H2 antibody essentially redirects the lupus immune machinery toward cancer.

❓ What About Antihistamines?

A logical question might be: if lupus involves inflammation, would antihistamines help control these immune responses?

The short answer: not in this case.

Histamines and interferons are completely different immune messengers. Histamines cause allergy symptoms like hives or sneezing and are blocked by antihistamines. Interferons, however, are part of the innate immune system’s antiviral and anticancer response and are not influenced by antihistamines.

So while antihistamines might help with some skin or allergy-like symptoms in lupus, they don’t regulate cGAS or interferon-driven inflammation, which is the pathway being activated to kill cancer cells in this study.

🧪 Testing for Interferons in Germany & the U.S.

Specialized interferon and cytokine testing is available through major laboratories in both Germany and the United States. These tests are often used in evaluating autoimmune diseases like lupus, or monitoring immune responses in cancer therapy and research.

🇩🇪 Germany – Key Labs and Codes

Lab	Test	Code (if known)
IMD Labor Berlin	Interferon-alpha Serum	1626
IMD Labor Berlin	Interferon-gamma Serum	1627
Synlab Germany	Interferon-gamma (TB)	18684
Synlab Germany	ANA-HEp-2	12136
MVZ Labor Dr. Reising-Ackermann	Interferon / Cytokine panel	Available by request

📌 Note: Most tests require a physician referral. You can request:

"Ich würde gerne meine Interferonwerte testen lassen, insbesondere Interferon-alpha, im Rahmen einer autoimmunologischen Abklärung."

🇺🇸 United States – Major Lab Providers

Lab	Test	Code / Notes
Mayo Clinic	Interferon Alpha (Serum)	Test ID: IFNA
LabCorp	Quantiferon-TB Gold (IFN-γ release assay)	Test code: 182879
Quest Diagnostics	Quantiferon-TB Gold Plus (IFN-γ)	Test code: 16358
Specialty Clinics/Academic Labs	Type I IFN Signature Panel	Research/Clinical Immunology Use

🧾 Note: The Type I Interferon Signature Panel, used to measure interferon-stimulated genes (ISGs), is not yet widely available through commercial labs but is offered at specialized centers (e.g., NIH, academic rheumatology clinics, etc.).

📍 Summary: Turning Disease Insight Into Therapeutic Innovation

This innovative study shows how a destructive autoimmune mechanism — like those seen in lupus — can be repurposed as a targeted tool against cancer. By understanding and redirecting the immune system's most potent weapons, researchers may unlock a new class of immunotherapies that don’t just treat cancer but do so with precision and immune intelligence.

As diagnostic labs catch up to this research, both clinicians and patients may benefit from advanced interferon testing, better immune profiling, and personalized immunotherapy strategies — potentially guided by insights from diseases like lupus.

Search This Blog

Q and A: about health and research