New Universal Therapy Effective in Multiple Tumor Types

Glycans' Abundance on Cancer Cells May Be Their Undoing

by [Arkadi](#) - September 26, 2025

Scientists have reported a breakthrough using a Velcro-like tool that targets glycans, surface sugars especially abundant in cancer cells. This potentially off-the-shelf therapy does not require adjustment to individual cancer types or patients. Key highlights of this new therapeutic approach include:

• Cancer cells have more sugar molecules: These glycans are more abundant on cancer cells than on normal cells.
• Targeting of glycans: Utilizing glycans allows for efficient targeting of cancer cells, enabling focused delivery of therapeutic agents.
• T cell recruitment: This method facilitates the direct engagement of T cells to cancer cells, enhancing immune response.

No Sugarcoating This

Antibody-based cancer immunotherapies, such as chimeric antigen receptor T (CAR-T) cells, were once heralded as game-changers in oncology. Despite their potential, several significant hurdles remain:

• On-target, off-cancer toxicity: High-affinity antibodies can damage normal tissues, leading to serious side effects.
• Specificity issues: Current therapies often require customization for specific cancer types, which leads to increased costs and complexity.

One of the most prevalent adaptations that help cancer cells to thrive and evade immune response is a remodeled glycocalyx, which consists of glycans linked to proteins and fats (glycoproteins, glycolipids, proteoglycans) ^[3]. Tumors often thicken and re-pattern these sugars into tumor-associated carbohydrate antigens (TACAs), creating barriers that can hide danger signals from immune cells and facilitate tumor growth.

The Two-Armed Bandit

The researchers at the University of California Irvine developed sugar-binding proteins called lectins, which act to amplify weak grips to form a strong adhesive surface (avidity). This innovation is likened to Velcro instead of relying on a single high-affinity key-lock connection typical of antibodies.

A bispecific protein was created that fuses a lectin carbohydrate-recognition domain (CRD) to a single-chain antibody. This design allows one arm of the protein, containing four lectins, to latch onto the glycans on cancer cells, while the other arm attaches to a T cell, effectively bridging the two:

Dr. Michael Demetriou, MD, Ph.D., stated, “It’s the holy grail – one treatment to kill virtually all cancers.” This innovative dual-targeting strategy effectively distinguishes between cancerous and healthy cells while combating cancer’s immune evasion tactics.

Effective Against Multiple Cancers

The GlyTR constructs, GlyTR1 and GlyTR2, exhibited significant efficacy against a range of cancers, including:

• Breast
• Ovarian
• Prostate
• Pancreatic
• Colon
• Lung
• Acute Myeloid Leukemia (AML)
• Myeloma
• T-cell leukemia

Notably, conventional immunotherapy predominantly yields success in blood cancers; however, GlyTR technologies demonstrated significant potential in targeting solid tumors. The researchers validated their approach using immunodeficient mice, which were implanted with human tumors. Following the injection of fluorescent GlyTRs, the constructs localized to the lungs hosting metastatic triple-negative breast cancer while avoiding healthy tissue, underscoring the tumor-specific targeting capability.

Future Perspectives

In models of triple-negative breast cancer, pancreatic, and ovarian cancers, GlyTRs exhibited dramatic responses, effectively halting tumor growth compared to treatments using only human CD8+ T cells. The ovarian cancer model's success was subsequently replicated at the National Cancer Institute (NCI), setting the stage for future clinical trials.

Given these promising results, the development of clinical-grade GlyTR1 proteins is underway at the NCI Experimental Therapeutics program with human trials expected to commence within two years. According to Dr. Farshid Dayyani, MD, Ph.D., “This is the revolutionary approach to cancer treatment our patients have been waiting for.”

Literature

• [1] Zhou, R. W., et al. (2025). Safe immunosuppression-resistant pan-cancer immunotherapeutics by velcro-like density-dependent targeting of tumor-associated carbohydrate antigens. Cell, 188, 1–17.
• [2] Lamers, C. H., et al. (2013). Treatment of metastatic renal cell carcinoma with CAIX CAR-engineered T cells: clinical evaluation and management of on-target toxicity. Molecular Therapy, 21(4), 904-912.
• [3] Buffone Jr, A., & Weaver, V. M. (2019). Don’t sugarcoat it: How glycocalyx composition influences cancer progression. Journal of Cell Biology, 219(1), e201910070.

Support Our Work: We are a non-profit foundation and rely on contributions to maintain independent journalism. Every donation, big or small, helps us continue our mission. Thank you for your support!