Vaccines Targeting This Protein Could Treat a Variety of Cancers

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As cancer immunotherapy has advanced over the past few years, an increasing number of research teams have turned their attention to developing cancer vaccines, which are a form of active immunotherapy that works by triggering the body’s defenses against cancer by exposing patients to the appropriate antigens found in tumor cells. Currently, some of the cancer vaccines that we are aware of are preventive vaccines, like the human papillomavirus (HPV) vaccine to prevent cervical cancer. However, therapeutic cancer vaccines remain the scientific community’s unattainable goal in a world where cancer is still a hot topic.

Professor Arjan Griffioen of Vrije Universiteit Amsterdam has long been working on developing cancer vaccines. As early as 2006, his team discovered that a protein called Vimentin is closely related to the malignant degree of tumor cells. Vimentin is the most important type of intermediate fibrin, a crucial skeletal protein connecting the cell membrane and nucleus. The team discovered that vimentin is overexpressed in tumor blood vessels and is present in the blood that feeds tumors. Further investigation revealed that vimentin suppresses the immune system while also assisting in the growth of new blood vessels that support tumor growth.

Professor Arjan Griffioen devised a strategy aimed at blocking the production of vimentin in tumors by combining self-antigens with engineered bacterial proteins for immunization. The cancer vaccine, named after Griffioen, showed favorable immune responses in mouse models of skin, brain, and rectal cancers. Animal experiments have shown that the Griffioen vaccine extends the lifespan of animals by an average of one year, which is more effective and cheaper than existing immunotherapy and has few side effects.

In May 2022, Professor Arjan Griffioen’s team published a new research paper entitled: Extracellular vimentin mimics VEGF and is a target for anti-angiogenic immunotherapy in Nature Communications. They further confirmed that vimentin is a vascular immune checkpoint molecule. Targeting this protein could provide a “double-edged sword” effect. 

The latest research has once again shown that tumor endothelial cells externalize vimentin to support angiogenesis while protecting blood vessels from leukocyte contact and thwarting immune responses. Importantly, tumor vascularization and tumor growth have been specifically and safely inhibited by extracellular vimentin-targeting passive and active antibody immunotherapies. Several preclinical model experiments have proven this.

In the new experiment, the research team treated 35 pet dogs with spontaneous transitional cell carcinoma of the bladder with the Griffioen vaccine. Half of the dogs were still alive after 400 days of treatment, and two others had fully recovered.

In addition, they treated a 10-year-old Belgian Malinois named Rax. It has osteosarcoma with a poor prognosis, and was nearing the end of its lifespan. Rax was the first osteosarcoma patient (dog) to be vaccinated against Griffioen. After more than three months of treatment, the tumor disappeared and Rax appeared to be back to normal.

According to the researchers, polyclonal responses brought on by vaccination may be more effective than monoclonal antibodies, which have grown to be a crucial component of tumor therapy. Because the broader polyclonal reactivity can more effectively inhibit vimentin’s extracellular function, it can also more effectively induce complement-dependent cytotoxicity and antibody-dependent cytotoxicity, boost anti-tumor immunity, and harm tumor blood vessels.

The majority of the known vaccination side effects to date have affected the area where the shot was administered. Animals may also experience discomfort or fever, but these symptoms will go away on their own in 3 to 5 days. This cancer vaccine is therefore secure.

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