A team of international researchers has developed a new cancer vaccine with the ability to overcome a tumor’s defense system.
While a cure for cancer has kept the research world on its toes for decades, recently scientists have shifted their attention to cancer vaccines. Over the past few years, thanks to the emergence of mRNA technology, researchers have developed several different vaccines targeting various types of cancers. While some are in just the development phase, many have begun clinical trials in humans. Now, researchers at the Wyss Institute and Dana-Farber Cancer Institute (DFCI) seem to have taken things one step further by designing a new cancer vaccine that can likely work against resistant tumors. The team outlined their research in the journal Nature.
This approach has great potential to treat patients suffering from a number of types of cancer, and really demonstrates the power of combining fundamental immunology insight with new technologies developed at the Wyss.
Dr. Dave Mooney, study co-author
Cancer is not an easy disease; neither for the patient going through it nor the doctor treating it. According to the World Health Organization (WHO), cancer accounted for nearly 10 million deaths in 2020. While there are more than 200 types of cancers in the world, lung, breast, colon, and rectum cancer are the most common out of all. Moreover, lung and colon cancer accounted for the most common causes of cancer-related death in 2020.
Current options for cancer treatment includes chemotherapy, radiotherapy, surgery, hormonal treatments, immunotherapy, and often a combination of the mentioned options. However, despite it all, tumors often become resistant to treatments and metastasize to other organs in the body. This increases mortality and makes it more difficult to effectively treat the patient.
Therefore, researchers are turning towards cancer vaccines to prevent and protect against highly metastatic tumors. However, vaccines are often tailored according to the type of cancer they are targeting.
How Does it Work?
Typically, cells with damaged DNA exhibit a protein on their surface that signals the T cells and natural killer (NK) cells to come and destroy them. These T and NK cells attach to the MICA and MICB proteins on the tumor’s surface. However, cancer cells often slice off these proteins; thus, evading detection and destruction by the immune system.
Now, led by Dr. Kai Wucherpfennig, the team of researchers have figured out a way to overcome this defense mechanism. In the past, researchers developed cancer vaccines that targeted peptide antigens present on a tumor’s surface. Although effective, these vaccines are often limited by their individuality. In a bid to overcome these defenses, the team developed a generalized vaccine that can work against various types of cancers and ultimately benefit more people.
The vaccine works by preventing the shedding of the MICA and MICB proteins and increasing their density. Thus, enabling the T and NK cells to go and destroy them.
Notably, this vaccine maintains efficacy against … tumors resistant to cytotoxic T cells through the coordinated action of NK cells and CD4+ T cells. The vaccine is also efficacious in a clinically important setting: immunization following surgical removal of primary, highly metastatic tumors inhibits the later outgrowth of metastases.
study authors
The vaccine has not yet undergone human testing. However, researchers have tested its safety and efficacy in animal models. Based on the results, the team now plans to trial the vaccine in human patients.
Other Cancer Vaccines in the Works
The team tested the vaccine in mouse and rhesus macaque models of melanoma and triple-negative breast cancer. Both these tumors often metastasize, even post-surgery. Moreover, both are highly resistant to current cancer treatments.
As part of the study, researchers first surgically removed the tumors from the mice and then administered the vaccine. Much to their surprise, the vaccine greatly reduced the rate of metastasis of the cancers. Moreover, four months later, the researchers exposed some of the vaccinated animals to cancerous tumors and none developed the disease. Thus, demonstrating the vaccine’s effectiveness.
This vaccine design enables protective immunity even against tumours with common escape mutations.
study authors
The study authors believe that the vaccine will likely perform better in combination with radiation therapy. Furthermore, since the vaccine relies on both T and NK cells, it can likely help treat cancers that are resistance to other types of cancer vaccines.
This is not the first time that researchers have worked on a cancer vaccine that targets hard-to-treat cancers. Recently, BioNTech began phase II trials of its mRNA vaccine for colon cancer. The mRNA vaccine aims to prevent relapse in patients at high risk.
Another mRNA vaccine is also in the clinical trial phase. According to BioNTech, the mRNA cancer treatment targets advanced solid tumors. The treatment when tested in animal models of melanomas and lung cancer, caused a shrinkage of the tumor and also targeted secondary tumors.
The emergence of new vaccine technology reveals that cancer might soon become a treatable and preventable illness.
Reference:
Soumya Badrinath et al, A vaccine targeting resistant tumours by dual T cell plus NK cell attack, Nature (2022). DOI: 10.1038/s41586-022-04772-4
