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Hope For Patients With Aggressive Breast Cancer: Vaccine Trial Results In 88% Survival Rate After 3 Years

Study author William Gillanders – credit, SWNS

Breast cancer patients have been given fresh hope after a new vaccine showed "promise" in treating an aggressive form of the disease.

The results came in a clinical trial involving American patients with triple-negative breast cancer who received an experimental drug designed to prevent the recurrence of tumors.

The trial, using a therapy designed by researchers at Washington University School of Medicine in St. Louis, is the first to report results for a "neoantigen DNA vaccine" for breast cancer patients.

The findings, published in the journal Genome Medicine, showed the vaccine to be "well-tolerated" and to properly stimulate the immune system.

The trial involved 18 patients diagnosed with a yet-to-metastasize triple-negative breast cancer. Each patient received the standard of care and three doses of a personalized vaccine tailored to target key mutations in their specific tumor and train immune cells to recognize and attack any cells bearing the mutations.

Following treatment, 14 of the 18 patients showed immune responses to the vaccine and, after three years, 16 patients remained cancer-free.

While the early-stage trial was designed to evaluate the safety of the vaccine and did not include a control group to determine efficacy, the research team analyzed historical data from patients with triple-negative breast cancer treated with the standard of care only.

In that group, on average, only about half of patients remained cancer-free three years after treatment.

Study senior author Professor William Gillanders, of Washington University School of Medicine, admits it's not a perfect comparison, and says there are key limitations of this type of analysis.

"But we are continuing to pursue this vaccine strategy and have ongoing randomized controlled trials that do make a direct comparison between the standard of care plus a vaccine, versus standard of care alone," he said.

"We are encouraged by what we're seeing with these patients so far."

Triple-negative breast cancer is an aggressive tumor type that grows even in the absence of the hormonal fuel that drives the growth of other types of breast cancer. It currently has no targeted therapies and is usually treated with traditional approaches including surgery, chemotherapy, and radiation therapy.

For the trial, patients with triple-negative breast cancer who still had evidence of a tumor remaining after a first round of chemotherapy were eligible to participate.

Researchers say such patients are at "high risk" of cancer recurrence even after the remaining tumor is surgically removed.

After surgery, the team analyzed and compared the tumor tissue with the healthy tissue of the same patient to find unique genetic mutations in the cancer cells.

These may alter the proteins only in the tumor, making it possible to train the immune system to go after the altered proteins and leave healthy tissues alone.

Using software they designed, the researchers selected altered proteins called neoantigens that were made by the patient's tumors and that were identified as most likely to trigger a strong immune response.

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On average, each patient's vaccine contained 11 neoantigens—ranging from a minimum of 4 to a maximum of 20—all of which were specific to their tumor.

"These are complex algorithms, but in general, the software takes in a list of mutations and interprets them in the context of their potential to be good neoantigen candidates," said Professor Malachi Griffith, who co-led the software development.

"The tools rank the possible neoantigens based on our current knowledge of what matters in stimulating the immune system to attack cancer cells."

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Several studies of cancer vaccines developed at Washington University School of Medicine are currently ongoing.

In some of the trials for breast cancer patients, personalized vaccines are being investigated in combination with immunotherapies called checkpoint inhibitors that boost the action of T cells.

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How Wearable Tech Can Help Women Fight Breast Cancer

Although she is concerned about the accuracy of wearable devices without a specialist overseeing the process, she believes they could be a game-changer for many women. "It is important to continue raising awareness about early detection and to support advancements in technology that can make the process easier and more accessible for everyone," she says.

According to the Global Cancer Observatory (GCO) and the International Association of Cancer Registries (IACR), breast cancer is the most commonly diagnosed cancer worldwide and is the leading cancer among women. Early detection of abnormal breast tissue changes is crucial for improving survival rates and minimizing the need for aggressive treatments. Wearable technology is becoming increasingly important in this effort, offering devices that monitor breast tissue changes, encourage self-screening, track treatment side effects, and support rehabilitation by monitoring physical activity, all of which can lead to earlier interventions and better patient outcomes.

MIT researchers have developed a wearable ultrasound device that helps detect tumours in their early stages. The flexible device can be attached to a bra, allowing users to move an ultrasound tracker across it to capture images of breast tissue from multiple angles. "The device is based on the same ultrasound technology used in imaging centres. However, its piezoelectric-based materials allow it to be miniaturized into a portable ultrasound scanner. Piezoelectricity is a process in which crystals convert mechanical energy into electrical energy, which in this case, can then be interpreted for ultrasound readings," explains Dr Jyoti Anand, a senior consultant, medical oncology at Fortis Hospital, Noida.

How would it work?

This wearable ultrasound device, designed by MIT's Canan Dagdeviren, associate professor at MIT's Media Lab and the senior author of the study Conformable Ultrasound Breast Patch for Deep Tissue Scanning and Imaging, which appeared in Science Advances in July, 2023, could be particularly useful for patients at high risk of developing breast cancer between routine mammograms. Interval cancers, which arise between scheduled screenings, account for 20-30% of all breast cancer cases. Inspired by her late aunt's battle with late-stage breast cancer, Dagdeviren believes this device could potentially save 12 million lives annually.

Currently, the wearable ultrasound device connects to standard ultrasound machines for imaging. However, the researchers are developing a smartphone-sized version for more portable and user-friendly breast tissue monitoring. This device offers real-time, continuous tracking, which could be especially helpful for those without regular access to screenings and for monitoring rapid changes during treatment. "When we visit a clinic for breast ultrasound, a doctor has limited time to screen that particular patient and limited motion of the probe. In this scenario, such devices can help. Having said that, the results from this device need to be monitored by a radiologist to maintain proper quality metrics. It still needs a lot of validation for interpretation of results and to recommend actions based on the report," says Dr. Anand.

Dr. Anand mentions another technique that is easy to use and helps in screening-thermography, also called infrared imaging: "The main principle of IR image diagnosis is that the unregulated growth of cells generates a higher metabolic rate and requires more blood flow than the surrounding tissue." The additional heat generated is delivered to the tissue surrounding the tumour, causing a temperature spike on the breast surface. This temperature spike is observed using IR imaging to detect the tumour.

Although breast cancer survival rates have improved, 50% to 96% of women experience weight gain during treatment. This can result from chemotherapy side effects, endocrine therapies, reduced energy expenditure, and is more common in premenopausal women. For breast cancer patients, monitoring key symptoms and health metrics during treatment is essential for effective management and improving outcomes. "Key aspects include tracking blood sugar levels, particularly in diabetic patients, as elevated glucose can complicate cancer control," says Dr. Mandeep Singh Malhotra, Director of Surgical Oncology at CK Birla Hospital, Delhi.

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Sensitive sensors

Along with MIT's device, Nevada, USA-based health-tech company Cyrcadia Health has also developed a non-invasive wearable device, essentially a bra insert called the iTBra, which consists of two intelligent breast patches worn for a few hours daily. The Cyrcadia Breast Monitor tracks changes in skin surface temperature to detect early breast anomalies using a four-dimensional system (time, temperature, and sensor x and y location). The device connects to a PC or mobile app, where anonymized data is processed to provide accurate, automated results for healthcare providers. The device has recently entered the first phase of clinical trials.

Monitoring recovery

Tracking health has become easier with wearable fitness devices, which help cancer patients and care teams monitor activity and vital health data for quicker adjustments to treatment plans. Many wearables also sync with mobile apps, allowing patients to easily log symptoms, medication, and diet. "By providing alerts for abnormal readings—such as high blood sugar or low white blood cell counts—these devices empower patients to communicate proactively with their healthcare providers. Furthermore, wearables can encourage healthier lifestyle choices, reminding patients to stay active and adhere to treatment regimens, ultimately leading to improved health outcomes," says Dr. Malhotra.

  The increasing sophistication of wearable tech holds great potential to improve the care and management of breast cancer patients, says the doctor. "Essential developments include advanced smart glucose monitors that not only track glucose levels but also analyze trends and recommend dietary adjustments. Devices that monitor body mass index (BMI) could track changes in muscle mass and fat, providing insights into the patient's nutritional status. Additionally, comprehensive symptom tracking applications would allow patients to log symptoms, side effects, and medication adherence, facilitating better communication with healthcare providers" he explains.

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Telehealth solutions could also enhance access to care, particularly for patients in rural areas, while AI-driven health analytics could identify patterns and predict complications, enabling personalized care strategies. "Lastly, behavioural support platforms that offer resources for mindfulness, stress management, and coping strategies can significantly enhance patients' emotional well-being throughout their cancer journey," says Dr Malhotra. Investing in these innovations can lead to a more holistic approach to breast cancer care, ultimately improving patient quality of life and outcomes, says doctors. Though these devices are not on the market yet, tech companies are racing to make them available and can be pathbreaking for the future of cancer treatment.

Aditi Sarawagi is an independent writer who covers wellness, travel and food.

Neoantigen DNA Vaccines Improve Survival And Immunity In Triple-negative Breast Cancer Patients

Researchers unveil a groundbreaking DNA vaccine that supercharges immunity and boosts survival in patients with aggressive breast cancer—could this be the future of personalized cancer treatment?

Study: Neoantigen DNA vaccines are safe, feasible, and induce neoantigen-specific immune responses in triple-negative breast cancer patients. Image Credit: Nemes Laszlo / Shutterstock

In a recent study published in the journal Genome Medicine, researchers in the United States of America developed a neoantigen deoxyribonucleic acid (DNA) vaccine platform and conducted a phase 1 clinical trial to assess its safety and immune response in patients with a high risk of triple-negative breast cancer (TNBC). They found that the vaccine was well tolerated, induced neoantigen-specific T-cell responses in 78% of patients, and showed a promising recurrence-free survival rate of 87.5% over 36 months, compared to 49% in historical controls.

Background

Tumor-expressed mutant proteins that can be recognized by the immune system, called cancer neoantigens, are promising targets for immunotherapy. Advances in cancer sequencing and bioinformatics have enabled the identification of these neoantigens, leading to the development of vaccines that stimulate neoantigen-specific T-cell responses and antitumor immunity. Initial studies demonstrated the efficacy of neoantigen vaccines in preclinical models and human melanoma using various platforms, including dendritic cells, synthetic long peptide (SLP), and ribonucleic acid (RNA) vaccines. While these approaches have shown promise, the DNA vaccine platform offers unique advantages, including design flexibility, lower cost, and the ability to include multiple neoantigens in a single construct.

Neoantigen vaccines have also been evaluated in glioblastoma, pancreatic cancer, and other malignancies, proving safe and immunogenic in early trials. TNBC lacks targeted therapies and is associated with a high mutational burden and abundant tumor-infiltrating lymphocytes (TILs), which correlate with better outcomes. These features make TNBC an ideal candidate for neoantigen vaccine therapy. Despite this potential, no neoantigen DNA vaccine studies had been reported in breast cancer until this study. In the present study, researchers developed a neoantigen DNA vaccine platform enhanced with electroporation for improved immunogenicity. They investigated its effects via a phase 1 clinical trial in patients with persistent TNBC after chemotherapy.

About the Study

A total of 35 patients with persistent TNBC following neoadjuvant chemotherapy and without metastatic cancer or autoimmune disorders were enrolled between 2015 and 2018. Tumor biopsies and matched peripheral blood mononuclear cells (PBMCs) were collected for tumor-normal exome sequencing to detect somatic mutations and neoantigens. Neoantigens were identified using the pVACtools pipeline, which prioritized peptides based on binding affinity, expression, and mutation characteristics. DNA vaccines were designed to target prioritized neoantigens, incorporating a mutant ubiquitin sequence to enhance antigen presentation. Human leukocyte antigen (HLA) typing and validation assays ensured precise epitope targeting. Each vaccine underwent rigorous quality control, ensuring sterility and expression capability.

Seventeen subjects were excluded from treatment due to complete pathologic response, ductal carcinoma in situ, insufficient tumor tissue, patient preference, or disease recurrence. Eighteen patients received the vaccine, targeting a median of 10 neoantigens (4–20) after completing standard adjuvant therapy. The vaccine (4 mg) was administered intramuscularly using the TriGrid electroporation device on days 1, 29, and 57. To measure T-cell responses, peripheral blood was drawn for immunological assessments, including ELISpot and flow cytometry. Safety monitoring included clinical and laboratory evaluations. Toxicity was graded per the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE). Immune responses were confirmed using enzyme-linked immunosorbent spot assay, flow cytometry, and tetramer staining, followed by T-cell receptor (TCR) sequencing and clonotype analysis. Statistical analysis involved the use of Student's t-test, Kaplan–Meier product-limit method, and log-rank test.

Design, manufacture, and administration of neoantigen DNA vaccines for TNBC patients. A Somatic mutations were identified by whole exome sequencing of tumor and germline DNA. Mutation expression was confirmed by tumor RNA-seq with cDNA capture. Candidate neoantigens were prioritized for inclusion in the vaccines on the basis of HLA binding predictions by pVAC-seq (Methods). Neoantigen DNA vaccines were administered intramuscularly using a TriGrid electroporation device. Peripheral blood was drawn prior at each vaccination timepoint and at selected timepoints after all vaccinations as indicated in A. B 35 patients with locally advanced TNBC were consented. Patients were excluded due to complete pathological response after neoadjuvant chemotherapy (NAC), insufficient tumor, patient withdrawal, and disease recurrence. 18 patients received personalized neoantigen DNA vaccines

Results and Discussion

A median of 21.5 somatic mutations was found per patient, eight of which led to the identification of candidate neoantigens. Most of these mutations were missense mutations, with TP53 mutations being prevalent. The inclusion of TP53-related neoantigens highlights the potential of targeting common driver mutations in TNBC. The vaccines included a median of 10 neoantigens, ranging from 4 to 20 per patient.

Forty-five out of 47 neoantigens that induced an initial response were confirmed as immunogenic. A total of 14 patients showed a response to at least one neoantigen, with 23% of the 198 total neoantigens being immunogenic. After vaccination, a marked increase in the number of spot-forming cells (SFCs) was observed in patients, indicating an expanded neoantigen-specific immune response. Flow cytometry analysis revealed both CD8 and CD4 T-cell responses to the neoantigens. The expansion of neoantigen-specific TCRs following vaccination was further confirmed, with some neoantigens showing monoclonal responses and others demonstrating oligoclonal expansion.

Clinical outcomes were assessed by comparing recurrence-free survival (RFS) in vaccinated patients to historical TNBC controls. After 36 months, vaccinated patients had an RFS of 87.5%, significantly higher than the 49% observed in the control group (P = 0.011). Vaccination was well tolerated, with one grade 3 event (hypertension) and 13 grade 2 events (injection site pain), along with mild myalgia (grade 1).

Overall, the study suggests that personalized neoantigen DNA vaccines are feasible, well-tolerated, and capable of inducing robust immune responses and improving clinical outcomes in TNBC patients. Although the trial was not randomized and comparisons to historical controls have limitations, the observed improvements in RFS strongly support further exploration of this approach.

Conclusion

In conclusion, the neoantigen DNA vaccine platform approach offers a promising, personalized immunotherapy strategy that could also be extended to other cancers with low mutation burdens, potentially improving outcomes in difficult-to-treat malignancies. Future studies combining these vaccines with immune checkpoint inhibitors may further enhance therapeutic efficacy.

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