Study: Personalized vaccines may help pancreatic cancer treatment

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Strength of Science: Medium-High

Research Timeline: Human Research

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What is this study about?

A personalized vaccine as treatment for pancreatic cancer was tested in this study with a small group of participants. The vaccine was custom-made for patients based on the unique features of their cancer. It was given in addition to a drug that affects the immune system and standard chemotherapy,  Researchers focused on patients who had surgery for their pancreatic cancer and hoped to increase the time before the cancer returned while also improving patient survival.

Why is this study important?

Pancreatic cancer typically has a low survival rate and is the third-leading cause of cancer deaths in the US. Pancreatic cancer cases have been rising in the US and worldwide. With few effective treatments available, better therapies are needed.

One promising treatment approach is immunotherapy, which uses the body’s immune system response to target cancer cells. Vaccines can improve the immune system’s ability to find and kill cancer cells. However, standard immunotherapy drugs for pancreatic cancer has not been helpful  in studies to date.

Researchers wanted to see if they could create a vaccine (based on the relatively new processes also used with the COVID vaccines) that increases certain immune system cells known as CD8+ T cells in pancreatic cancer patients. This vaccine uses a substance called mRNA (messenger RNA) from the cancer to help stimulate the immune system. They hope that this vaccine will trigger a better immune response by increasing the number of  CD8+ T cells that can target and kill cancer cells.

Study findings

Sixteen study participants with pancreatic cancer had surgery to remove their tumors and were treated with the mRNA vaccine, an immunotherapy drug and chemotherapy.  

The vaccine improved the immune system response.

• Half (8 of 16) of the people who received the vaccine had more CD8+ T cells after treatment than they did before the treatment. The researchers referred to these patients as “responders” because their immune systems responded to the vaccine by making more immune cells that could target their pancreatic cancer.  

The vaccine extended the time before the cancer returned.

• Most responders had no return of their cancer at 18 months after treatment.
• At the time this research was reported, some responders’ cancer had still not returned.
• Among non-responders (participants whose immune cells did not increase after vaccination), cancer returned about 11 months after the end of their vaccine treatment.
• The delay in cancer recurrence was most closely tied with the amount of the immune response rather than other factors, such as features of the patients themselves, chemotherapy drugs used or tumor size.

The immune response could last as long as 2 years.
Researchers assessed the number of CD8+ T cells in participants several times after treatment:

• Responders had more CD8+ T cells for up to two years after treatment.
• The CD8+ T cells were able to attack cancer cells in the pancreas and cancer cells that had spread to other parts of the body. In one patient, a liver metastasis occurred. When it was biopsied, It found  surrounded by many CD8+ T cells. Later, the metastasis disappeared on CT imaging.

Side effects associated with the vaccine were minimal.

• No participants had a serious (grade 4 or 5) or life-threatening adverse event.
• One person had a serious grade 3 fever and high blood pressure.

Most participants had low-grade side effects. The most common were chills and fever linked to the vaccine and itching linked to the immunotherapy drug.

What does this mean for me?

Although promising, this is an early research study involving only a few people. Vaccines and other immunotherapies to treat pancreatic cancer are currently only available through a clinical trial. The phase 2 clinical trial is enrolling participants for this drug. Larger research studies are needed to better understand the vaccine’s effectiveness and why some people respond and others do not. If you have been diagnosed with pancreatic cancer and you are interested in a vaccine for treatment, ask your doctor whether participating in a clinical trial is right for you. Some vaccine clinical trials for treating pancreatic cancer are included in this review under the tab marked “Research.”

In this small study, none of the participants tested positive for an inherited mutation, so it is unclear whether people with an inherited mutation that is linked to cancer would respond differently than other participants. Further research is needed to clarify this issue.

Reference

Rojas, L.A., Sethna, Z., Soares, K.C. et al. Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer. Nature 618, 2023; 144–150.

Disclosure: FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.

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posted 8/2923

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