Cancer Vaccine Improves Antigen Visibility in Tumors

A research team at Tufts University has developed a cancer vaccine that enhances the immune system’s ability to recognize and attack solid tumors. Unlike traditional vaccines that target specific antigens, this approach relies on a mix of tumor-derived protein fragments, known as a lysate, making it adaptable to a wide range of cancers. The vaccine, tested in animal models, demonstrated efficacy against melanoma, triple-negative breast cancer, Lewis lung carcinoma and inoperable ovarian cancer.

Overcoming the challenge of tumor antigen recognition

Therapeutic cancer vaccines aim to stimulate an immune response against existing tumors, but their development has been hindered by the difficulty of identifying antigens that the immune system can recognize as foreign. Many tumors express proteins similar to normal cells, making them less visible to immune surveillance.

The Tufts team, led by postdoctoral researcher Yu Zhao and biomedical engineering professor Qiaobing Xu, developed a method to amplify tumor antigen visibility without needing to identify specific proteins. Their approach uses a two-step process: first, modifying tumor proteins with a molecule called AHPC to enhance antigen presentation, and second, packaging the modified proteins into lipid nanoparticles that deliver them to the lymphatic system, where immune cells are concentrated.

Enhancing antigen presentation to boost immune response

The AHPC molecule plays a crucial role by recruiting an enzyme that tags tumor proteins with ubiquitin, a signal that marks them for processing by antigen-presenting cells such as macrophages and dendritic cells. These cells then present tumor-derived antigens to cytotoxic T cells, which are responsible for attacking cancerous cells.

By encapsulating these modified tumor proteins in lipid nanoparticles, the researchers ensured efficient delivery to lymph nodes, the primary sites where immune responses are activated. This design improved the vaccine’s ability to stimulate T cells, leading to tumor suppression and reduced metastasis in animal models.

Potential impact on cancer treatment

The flexibility of this vaccine design could make it applicable to a wide range of solid tumors, including those of unknown origin. By avoiding the need for tumor-specific antigen selection, the approach could streamline vaccine development and expand treatment options for patients with hard-to-target cancers.

Future studies will assess the vaccine’s effectiveness in clinical trials and explore its potential in combination with existing therapies such as chemotherapy and immune checkpoint inhibitors. If successful, this strategy could offer a new tool for enhancing immune responses against cancer and reducing recurrence rates.

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