Experimental vaccine passes phase 1 safety trials

Experimental vaccine passes phase 1 safety trials

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Experts are working on creating vaccines for different types of cancer, including breast cancer. Alina Hvostikova/Stocksy
  • Breast cancer is currently the most frequently diagnosed cancer in the United States, and globally it is the world’s most prevalent cancer.
  • According to new phase 1 clinical trial data, a new plasmid DNA-based vaccine that is able to target a receptor in breast cancer appears safe.
  • The non-randomized study showed an increased immune response after vaccination in people with advanced-stage ERBB2-positive breast cancer.

According to the World Health Organization, 2.3 million women were diagnosed with breast cancer in 2020, and there were over 7.8 million women alive who had been diagnosed with breast cancer in the previous 5 years.

Being female is the biggest risk factor for breast cancer, but around 1{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} of breast cancers do occur in men. The treatment of breast cancer follows the same principles for both sexes.

Speaking to Medical News Today Dr. Kotryna Temcinaite, senior research communications manager at Breast Cancer Now explained:

“Breast cancer is not a single disease, which makes it more difficult to treat. There are many types of breast cancer and treatments that work well for some people, may not work as well for others. That’s why we need to undertake further research into the disease, develop [k]inder and smarter treatments.”

Now, new research led by Dr. Mary (Nora) L. Disis, at the University of Washington Medicine Cancer Vaccine Institute on an experimental vaccine against breast cancer has shown it generates a strong immune response to ERBB2—formerly called HER2—a key tumor protein.

The study is published in the journal JAMA Oncology

The completed study was a single-arm phase 1 clinical trial that followed 66 people ages 34 – 77 years who had advanced-stage ERBB2-positive breast cancer. Researchers analyzed the data twice—from January 2012 to March 2013 and from July 2021 to August 2022.

Participants were vaccinated with either 10ug, 100ug, or 500ug doses of the plasmid DNA vaccine every month for three months. The researchers measured blood immunity and vaccine toxicity at set time points and assessed the DNA persistence of the vaccine via biopsy samples taken from the vaccine site at 16 and 36 weeks.

The researchers noted the most common side effects associated with the injection, 33{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} recorded flu-like symptoms, and 36{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} fatigue.

Participants who received the higher vaccine doses of 100 μg and 500 μg demonstrated a stronger immune response than those who received the 10ug dose, but there was no significant difference between the immune responses to the 100ug and 500ug doses.

The research team also found DNA persistence at the injection site was greatest with the highest vaccine dose and that this DNA persistence was associated with more rapidly waning immunity.

The study’s lead author Dr. Disis explained that the problem with current breast cancer treatments is “disease recurrence after optimal treatment.” She said the disease recurred because a small amount of cancer remained undetected.

“Vaccines will stimulate T-cells which can be programmed to hunt down these last remaining cells in the body and kill them. Stimulating effective immunity is the only way I know we can sterilize the body from all breast cancer cells.”
— Dr. Mary (Nora) L. Disis

“Ideally, it would be great to prevent all cancers before treatment is needed. We have already made way with some vaccines in cancer prevention such as the hepatitis B vaccines against hepatocellular carcinoma and HPV against cervical cancer,” said Dr. Bhavana Pathak, board certified hematologist and medical oncologist at MemorialCare Cancer Institute at Orange Coast Medical Center, California, who was not involved in the study.

Exciting potential

Dr. Temcinaite believes a vaccine has “exciting potential” for treating breast cancer. However, she said that “Scientists must investigate what to include in a vaccine, to trigger the right immune response.”

Breast Cancer Now is currently funding research to design a new cancer vaccine, specifically targeting the protein p53.

Dr. Parvin Peddi, medical oncologist and director of Breast Medical Oncology at Providence Saint John’s Health Center and associate professor of medical oncology at Saint John’s Cancer Institute, California further explained to MNT:

“[T]his is the first study in my knowledge to examine a HER2 specific vaccine for patients with HER2 positive metastatic breast cancer who are in remission. Although it’s an early study and it was not compared directly to patients not receiving the vaccine, the survival of patients seen in this study is much more than expected with observation.”

Dr. Disis said she believes there is a “good chance” breast cancer vaccines will be in use in clinics in about 5 years.

“Clinical trials of breast cancer vaccines given alone or with other treatments have increased by about 25{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} in the last several years. There are many groups working on ‘next-gen’ vaccines with very effective delivery technologies and adjuvants,” she told MNT.

Dr. Pathak echoed similar thoughts. She called the current study a “building block showing an increase[d] immune response against specific targets for patients with cancer.”

“Once later phase trials are completed showing efficacy in addition to tolerability, we can potentially anticipate seeing vaccines in clinic,” she said.

But could similar vaccines be developed to treat other types of cancer? Dr. Disis said she believes that is where cancer treatment’s future is headed.

“[Yes.] At the UW Medicine Cancer Vaccine Institute we have programs in breast cancer, ovarian cancer, colon cancer, prostate cancer, and bladder cancer vaccines and ideas for others,” she elaborated.

However, experts have also expressed caution about the trial’s early results.

Dr. Temcinaite said it was “too early to tell whether treatment vaccines for cancer could replace other existing treatments.”

“If [vaccines] are proven to be successful, at first they are most likely to be used alongside existing treatments, until we have enough data to understand who can safely skip any particular step in breast cancer treatment.”
— Dr. Kotryna Temcinaite

Dr. Pathak also raised caution that this study has only been completed in people with breast cancer. “[M]ore studies will be needed to address the possibility of primary prevention,” she pointed out.

“In general, if the protein that is targeted by the vaccine is also found in [healthy] cells, it would be important to watch for autoimmune side effects. For example, heart muscle also has HER2 expression. Although no excess cardiac side effects were reported in this study, it would be important to watch that in larger studies,” Dr. Peddi added.

It is also important to understand how long the benefits of these vaccines may last. The immune response wanes after vaccination so, it would be interesting to understand if booster vaccines might be needed for some patients.

When asked about the next steps Dr. Disis told MNT that the remarkable results they got from the Phase I trial for the HER2 vaccine lays the ground for future studies.

“The next step is to formally test that observation. In the Phase II study, we will randomize HER2-low patients to receive the vaccine or an immune-stimulating agent. The endpoint will be whether we do prevent disease recurrence,” she said.

Dr. Temcinaite advised that these new vaccines might not work for everyone who receives a breast cancer diagnosis.

“[M]ore research to discover new ways to treat breast cancer and build our understanding of who will and who won’t benefit from particular treatments and why,” she said.

Senate passes funding bill despite vaccine mandate flap, averting shutdown

Senate lawmakers voted Thursday night to approve a bill that funds the government through Feb. 18, avoiding a government shutdown with roughly 24 hours to spare despite a partisan clash regarding President Biden’s federal vaccine mandate.

The Senate voted 69-28 in favor of the continuing resolution, which approves government funding at the prior year’s levels until a new bipartisan agreement is reached. The resolution includes $7 billion in new funding to support Afghan refugees.

The bill now proceeds to Biden’s desk for final approval.

Senate Majority Leader Chuck Schumer, D-N.Y., arrives at the Capitol in Washington, Thursday, Sept. 30, 2021. (AP Photo/J. Scott Applewhite) (Associated Press)

“I am glad that in the end, cooler heads prevailed. The government will stay open,” Senate Majority Leader Chuck Schumer, D-NY, said. “And I thank the members of this chamber for walking us back from the brink of an avoidable, needless and costly shutdown.”

Moderate Democratic Sen. Joe Manchin of West Virginia was among the senators who voted in favor of the continuing resolution.

“In the midst of the COVID-19 pandemic and as the new Omicron variant emerges, I will not vote to shut down the government for purely political reasons,” Manchin said in a statement. 

A standoff between Senate Democrats and a handful of Republicans over the federal vaccine mandate nearly derailed the vote. Republican Sens. Ted Cruz of Texas, Mike Lee of Utah and Roger Marshall of Kansas demanded a separate vote on an amendment to bar funding for the Occupational Safety and Health Administration, the entity responsible for implementing Biden’s mandate. 

Schumer allowed the vote on the amendment to proceed ahead of the vote on the continuing resolution. 

Sen. Ted Cruz, R-Texas, speaks at a news conference on Capitol Hill in Washington, Wednesday, Oct. 6, 2021, to speak about immigration at the U.S.- Mexico boarder. (AP Photo/Andrew Harnik) (Associated Press)

Senators voted to reject Marshall’s amendment on the vaccine mandate. The amendment fell short of the 51 votes required to pass. Manchin and fellow moderate Democrat Sen. Kyrsten Sinema of Arizona each voted against the measure.

Republicans widely oppose the mandate, which forces companies with 100 or more employees to ensure their employees are vaccinated against COVID-19 or undergo regular testing. GOP lawmakers argue the mandate is too broad and constitutes federal overreach.

“No precedent exists in American history for punishing private employers who don’t enforcement government vaccination edicts,” Marshall said in a floor speech ahead of the vote on his amendment.

Lee said millions of Americans were “being threatened right now with losing their jobs” due to the mandate. He argued that Democrats, not Republicans, risked the shutdown in their effort to prevent a vote on the amendment.

“Those in this chamber who shamefully were refusing over and over again to even let us cast a vote on that simple measure threatened to shut down all of government because they didn’t want us to have a chance, as the people’s elected lawmakers, to decide whether or not we should proceed with vaccine mandate enforcement,” Lee said.

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Senate Minority Leader Mitch McConnell, R-Ky., arrives at the Capitol in Washington, Wednesday, Oct. 6, 2021, as a showdown looms with Democrats over raising the debt limit. (AP Photo/J. Scott Applewhite) (Associated Press)

The vote on the continuing resolution brought the Senate in sync with House lawmakers, who hours earlier voted 221-212 in favor of the continuing resolution to fund the government through Feb. 18. Rep. Adam Kinzinger, R-Ill., was the lone GOP representative to vote in favor of the resolution.

This story has been updated.