An effective combination cancer vaccine in mouse models

A new vaccine has been developed by scientists for cancer treatment. It combines chemotherapy and immunotherapy, and in mouse models, it has shown promise.

Laboratory results

A team of scientists recently created a new cancer therapy vaccine and it has shown promising results in mice, including in cancer that is difficult to treat.

The treatment requires a single injection of chemotherapy and immunotherapy that can open the door to personalized, highly effective, and easy-to-administer therapy.

Study published in the journal Nature Communications, will now need to switch to preclinical studies, which can then lead to human trials.

Cancer treatment

Chemotherapy and immunotherapy are two main approaches to treating cancer.

Chemotherapy aims to destroy cancer cells by preventing or reducing their growth, according to the National Cancer Institute (NCI).

However, it may also damage healthy cells, so it usually causes the person consuming it to have severe side effects. Tiredness, fatigue, hair loss, and mouth sores can be involved in these symptoms.

The NCI, on the other hand explains that immunotherapy mobilizes the immune system of an individual to target cancer cells.

Often without any assistance, the immune system can do this. Cancers, however are able to shield themselves from the immune system of a human. Immunotherapy helps improve the performance of the immune system.

Immunotherapy often has side effects, which can differ based on a person’s form of immunotherapy. In addition, immunotherapy usually has limited consequences for the most difficult-to-treat cancers, such as triple-negative breast cancer.

Triple-negative breast cancer does not stimulate strong responses from the immune system, and current immunotherapies have failed to treat it according to co-first study author Dr. Hua Wang, an assistant professor in the Department of Materials Science and Engineering at the University of Illinois at Urbana-Champaign.”

“In our system, the immunotherapy attracts numerous immune cells to the tumor while the chemotherapy produces a large number of dead cancer cell fragments that the immune cells can pick up and use to generate an effective tumor-specific response.”

The scientists behind the latest research are aiming to get the’ best of both worlds’ by combining the two cancer therapies.

Long-term research

In the new research, the treatment the team tested is the result of over 10 years of development.

In 2009, Robert P. Pinkas Family Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences in Cambridge, MA, a group led by corresponding study author Prof. David Mooney, announced that they had created an implantable cancer vaccine that showed promise in mouse models.

The vaccine operated by combining tumor-associated antigens (TAAs) that activate the immune response of the body with adjuvants that enhance the immune response efficacy. It results in a customized treatment of cancer that should be more effective.

Doing so however, requires either extracting antigens from the tumor of an individual or detecting antigens by genome sequencing, all of which are costly and take a large amount of time.

“One of the crucial limiting factors in the development of cancer vaccines is the selection of TAAs, according to co-first study author Alex Najibi, a graduate student in the laboratory of Prof. Mooney, “because we currently only have a very limited library of known antigens for a few unique tumor cell lines, and it is difficult to predict which can mount an efficient immune response.

“The implantation of chemotherapy drugs within the vaccine scaffold induces a burst of death of cancer cells that releases TAAs directly from the tumor into the dendritic cells, bypassing the long and expensive process of producing antigen.”

Combination vaccine

The researchers applied this technique to mice with triple-negative breast cancer and discovered that it allowed tumors to penetrate more effectively with chemotherapy drugs. This resulted in a rise in cancer cell deaths and fewer tumors being created.

The team then experimented with the addition of a third component, having succeeded in integrating chemotherapy and immunotherapy treatments into a single vaccine. This was a synthetic bacterial DNA sequence, which has been shown to enhance the immune response of the body in previous studies.

The researchers found that this additional component further decreased tumor growth and increased the mice’s life span.

The team observed a rise in the protein PD-L1 on the surface of the tumors of the mice while evaluating what effects the three-component vaccine had on the mice. To prevent detection by the body’s immune system, this protein is used by tumors.

Scientists saw even stronger results by injecting the mice with both the three-component vaccine and with an anti-PD-1 control point inhibitor, which inhibits the evasion of the immune system by a tumor.

Tumors in the mice were substantially reduced in size and number.

Furthermore the mice survived for an average of 40 days, compared with 27 days for mice not receiving any treatment and 28 days for mice only receiving the anti-PD-1 treatment.

Finally, the scientists saw that the mice had much lower tumor recurrence, slower tumor growth and improved survival rates after removing the triple-negative breast cancer tumors from the mice and treating them with the gel-based vaccine.

Significantly, none of them formed new tumors after the researchers reintroduced cancer cells to the mice they treated with the vaccine. In addition, the disease destroyed all the mice that did not receive the vaccine but received new cancer cells.

The team is now planning to continue refining the vaccine and in particular, to target other cancer forms that are difficult to treat as well. The scientists hope that their vaccine will move further forward into preclinical and then human trials.

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