Cancer Vaccines Individually Customized Using Patient’s Immune Cells

A HER2-targeted therapeutic cancer vaccine provided clinical benefit to several patients with metastatic HER2-positive cancers who had not previously been treated with a HER2-targeted therapeutic, according to National Institutes of Health (NIH) researchers. 

Targeted cancer therapies are drugs that block the growth and spread of cancer by interfering with specific molecules that are involved in the growth and spread of cancer, says the NIH.

Among 11 evaluable patients who had received more than the lowest dose of the vaccine, six (54 percent) had clinical benefit, reported this small, phase 1 clinical trial.  

This very limited study reported 1 patient with ovarian cancer had a complete response that lasted 89 weeks, one patient with gastroesophageal cancer had a partial response that lasted 16 weeks, and 4 patients had stable disease. 

The patients' vaccines are individually customized by these NIH researchers using their own immune cells isolated from their blood. The blood-derived immune cells are modified in several ways in the laboratory. 

The final product, which is administered between the layers of the skin, comprises patient-derived dendritic cells genetically modified with an adenovirus to produce parts of the HER2 protein. 

"Immunotherapy marshals the exquisite specificity of the immune system to destroy cancer, and some types may have potentially fewer side effects than traditional chemotherapy," said Jay A. Berzofsky, MD, PhD, chief of the Vaccine Branch at the Center for Cancer Research, National Cancer Institute, National Institutes of Health, in a press release.

"We are using a vaccine approach to generate an immune response to HER2, which is found at high levels on and drives the growth of several types of cancer, including breast, ovarian, lung, colorectal, and gastroesophageal cancers.”   

"Our results suggest that we have a very promising vaccine for HER2-overexpressing cancers," continued Berzofsky. "We hope that one day the vaccine will provide a new treatment option for patients with these cancers," said Dr. Berzofsky.  

In the dose escalation portion of the phase I clinical trial, patients were injected with the vaccine on weeks 0, 4, 8, 16, and 24 after enrollment in the study. Among the six patients who received the lowest dose of the vaccine, 5 million dendritic cells per injection, no clinical benefit was seen. 

Among the 11 patients who received either 10 million or 20 million dendritic cells per injection, six had clinical benefit. 

Adverse reactions were predominantly injection-site reactions that did not require treatment. No cardiotoxicity was seen. 

"Based on the current safety and clinical benefit data, the dose of the vaccine was increased to 40 million dendritic cells per injection and the trial opened to patients who have previously been treated with a HER2-targeted therapeutic, including patients with breast cancer," said Dr. Berzofsky. 

"Moving forward, we would like to investigate whether we can increase the proportion of people who benefit from treatment with the vaccine by combining it with checkpoint inhibitor therapy," he added. 

According to Dr. Berzofsky, the main scientific limitation of the study is that it is a relatively small, phase I clinical trial with no placebo control. However, the approach is sufficiently promising to warrant additional trials. 

Preclinical studies, which were previously published in the AACR journal Cancer Research, showed that this type of vaccine could eradicate large, established tumors as well as lung metastases in mice. 

This phase I clinical trial will be presented at the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival, held Sept. 30, 2018. 

This study was supported by intramural funds from the National Cancer Institute. Berzofsky declares no conflicts of interest.   

Media Contact: Julia Gunther [email protected]