Promising New Vaccine May Target All Types of Solid Cancer

Scientists have developed a groundbreaking cancer vaccine that trains the immune system to recognize and attack existing tumors. The technology modifies cancer proteins to make them more visible to immune cells and directs them to the lymph nodes, where the immune response is activated. In animal tests, the vaccine reduced tumor growth and prevented their spread, raising hope for more effective treatments.

Unlike traditional vaccines, which prevent diseases caused by viruses or bacteria, cancer vaccines are designed to treat an existing disease. Rather than preventing infection, they stimulate the immune system to recognize and attack cancer cells.

Some preventive cancer vaccines exist, but they generally target viruses linked to certain types of cancer, such as HPV, which is associated with cervical cancer.

The key to increasing the effectiveness of this new cancer vaccine lies in how it directs tumor-derived proteins to areas of the body where the immune system can recognize them most effectively.

Imagine that each tumor protein needs to be presented to the immune system, as if it were passing through a “police lineup” where the guards decide whether it is a suspect to be investigated. However, this process of “presenting” tumor proteins to immune cells is often inefficient.

To improve this process, the research team at Tufts University, USA, created a two-stage method. First, they modified the mixture of tumor proteins with a molecule called AHPC.

This molecule attracts an enzyme that adds a tag called ubiquitin to the proteins. Ubiquitin acts as a signal for the cell to process and break these proteins into smaller pieces, making it easier for them to be presented to the immune system.

Then, the researchers placed these modified proteins in small bubbles of fat, called lipid nanoparticles, which are designed to travel to the lymph nodes, where many cells that “present” antigens are located.

Once there, these cells process the fragments of tumor proteins and display them to the immune system, triggering a strong response from cytotoxic T cells, which are responsible for attacking and destroying cancer cells.

The cancer vaccine targets the lymphatic system and enhances its ability to recruit T cells to kill tumors. Here, three T cells (blue) are shown attacking and destroying a cancer cell. Credit: Yu Zhao

Tested in animal models of melanoma, triple-negative breast cancer, Lewis lung carcinoma, and inoperable ovarian cancer, the vaccine elicited a strong response from cytotoxic T cells, which attack growing tumors, suppressing their growth and metastasis.

This new approach to cancer vaccines represents a promising advance in immunotherapy by making the immune system more efficient at recognizing and attacking tumor cells.

By targeting tumor proteins for presentation more effectively, the strategy has shown positive results in reducing cancer growth and preventing metastasis in animal trials.

These findings suggest that in the future, this technology could be combined with other therapies to further enhance the effectiveness of treatment against a variety of cancers, offering new hope for patients and advances in the fight against the disease.

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Antitumour vaccination via the targeted proteolysis of antigens isolated from tumour lysates

Yu Zhao, Donghui Song, Zeyu Wang, Qingqing Huang, Fan Huang, Zhongfeng Ye, Douglas Wich, Mengting Chen, Jennifer Khirallah, Shuliang Gao, Yang Liu and Qiaobing Xu

Nature Biomedical Engineering, volume 9, pages 234–248 (2025)

DOI: 10.1038/s41551-024-01285-5

Abstract: 

The activation of cytotoxic T cells against tumour cells typically requires the cross-presentation, by antigen-presenting cells (and via major histocompatibility complex class I molecules), of an epitope derived from a tumour antigen. A critical step in antigen processing is the proteolysis of tumour antigens mediated by the ubiquitin–proteasome pathway. Here we describe a tumour vaccine leveraging targeted antigen degradation to augment antigen processing and cross-presentation. Analogous to proteolysis-targeting chimaeras, the vaccine consists of lymph-node-targeting lipid nanoparticles encapsulated with tumour antigens pre-conjugated with ligands that can bind to E3 ubiquitin ligases. In mice with subcutaneous human melanoma or triple-negative breast cancer, or with orthotopic mouse Lewis lung carcinoma or clinically inoperable mouse ovarian cancer, subcutaneously delivered vaccines prepared using tumour lysate proteins elicited antigen-specific adaptive immunity and immunological memory, and inhibited tumour growth, metastasis and recurrence, particularly when combined with immune checkpoint inhibition.