The method triggers immune responses that inhibit melanoma, triple-negative breast cancer, lung carcinoma, and ovarian cancer.
Cancer treatment vaccines have been in development since 2010, when the first was approved for prostate cancer, followed by another in 2015 for melanoma. While many therapeutic (rather than preventive) cancer vaccines have been researched since then, none have received approval. A major challenge in their development is identifying tumor antigens that are distinct enough from normal cells to trigger a strong immune response.
Researchers at Tufts University have now created a cancer vaccine designed to enhance the immune system's ability to recognize tumor antigens. This approach generates a powerful immune response and establishes long-term immunological memory, reducing the likelihood of tumor recurrence. Unlike traditional cancer vaccines that target specific antigens, this new vaccine utilizes a lysate—a mix of protein fragments derived from any solid tumor—eliminating the need to identify a single tumor-specific antigen.
The vaccine they produced worked against multiple solid tumors in animal models, including melanoma, triple-negative breast cancer, Lewis lung carcinoma, and clinically inoperable ovarian cancer.
Developed by a team led by Qiaobing Xu, professor of biomedical engineering, the method builds on earlier work expressing specific antigens for an enhanced immune response by making lipid nanoparticles that carry mRNA into the lymphatic system.
"We have significantly improved the cancer vaccine design by making it applicable to any solid tumor from which we can create a lysate, possibly even tumors of unknown origin, without having to select mRNA sequences, and then adding another component – called AHPC – that helps channel the protein fragments from the cancer cells into the immunological response pathway," said Xu.
How the Vaccine Works
Unlike traditional vaccines designed to prevent infectious diseases caused by bacteria or viruses, cancer vaccines work by stimulating the body's immune system to recognize and attack cancer cells. And unlike most vaccines against pathogens, they are designed to be therapeutic rather than preventive—acting to eliminate an existing disease. Some preventive cancer vaccines do exist, but they are generally targeted to viruses that are linked to cancers, such as HPV linked to cervical cancer.
The key to the increased potency of the new cancer vaccine lies in its ability to direct tumor-derived antigens into a cellular pathway that efficiently presents the antigens to the immune system. Think of the presentation as a kind of police lineup, where each antigen is presented for the immune system to decide if it can be considered a "suspect."
Rounding up the antigens and getting them into an antigen presenting cell like a macrophage or dendritic cell (the police stations, if we continue with the analogy) is generally an inefficient process for tumor antigens. This is where the Tufts research team applied a two-stage method to power up the process.
A Two-Stage Approach to Enhancing Immune Response
First, to make sure they round up all tumor proteins-of-interest, they modified the mix of tumor proteins with the AHPC molecule, which in turn recruits an enzyme to put a tag on the protein called a ubiquitin. It allows the cell to identify and process the protein into fragments for presentation to the immune system.
The researchers then packaged the AHPC-modified tumor proteins into tiny lipid (fat molecule) bubbles, specifically designed to home in on lymph nodes, where most of antigen presenting cells can be found.
Tested in animal models of melanoma, triple-negative breast cancer, Lewis lung carcinoma, and inoperable ovarian cancer, the vaccine elicited a strong response by cytotoxic T cells, which attack the growing tumors, suppressing further growth and metastasis.
"Fighting cancer has always been an arsenal approach," said Xu. "Adding cancer vaccines to surgical excision, chemotherapy, and other drugs used to enhance cytotoxic T cell activity could lead to improved patient responses and longer-term prevention of cancer recurrence."
Reference: "Antitumour vaccination via the targeted proteolysis of antigens isolated from tumour lysates" by 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, 28 November 2024, Nature Biomedical Engineering.
DOI: 10.1038/s41551-024-01285-5
The study was funded by the National Institutes of Health.
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