Measles Virus-Based Vaccine for Breast Cancer

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mayo Clinic

Must not be taking: Corticosteroids, others

Disqualifiers: Active infection, Heart disease, CNS metastases, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

Duration: 3-9 weeks

45 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial investigates the side effects and best dose of using a modified measles virus, MV-s-NAP, in treating patients with invasive breast cancer that has spread to other places in the body (metastatic). Both the unmodified vaccination measles virus (MV-Edm) and this modified virus (MV-s-NAP) have been shown to multiply in and destroy breast cancer cells in the test tube and in research mice. MV-s-NAP has been altered by having an extra gene (piece of deoxyribonucleic acid \[DNA\]) so that virus can make a protein called helicobacter pylori neutrophil activating protein (NAP) which is normally expressed in inflammatory reactions. Monitoring blood, urine, tissue, and throat swab samples, and using imaging tests may help to determine whether MV-s-NAP has any impact on the amount of disease present in metastatic breast cancer patients.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does mention that certain therapies and medications, like chemotherapy, immunotherapy, and HER2 directed therapy, must not have been taken recently. It's best to discuss your specific medications with the trial team to see if they might interfere with the study.

What data supports the effectiveness of the treatment MV-s-NAP for breast cancer?

Research shows that the MV-s-NAP treatment, which uses a modified measles virus, can effectively infect and destroy breast cancer cells, doubling the median survival time in a specific breast cancer model compared to a control group. Additionally, the treatment was well tolerated in preclinical safety assessments, showing no significant toxic side effects. ^{1 2 3 4 5}

Is the measles virus-based vaccine for breast cancer safe for humans?

In preclinical studies using a mouse model, the measles virus-based vaccine (MV-s-NAP) was well tolerated with no significant toxic side effects observed, supporting its safety for use in humans. ^{1 2 3 5 6}

How is the Measles Virus-Based Vaccine for Breast Cancer different from other treatments?

This treatment uses a modified measles virus to specifically target and destroy breast cancer cells while also boosting the immune response against the tumor. It is unique because it combines the virus with a protein from a bacteria (Helicobacter pylori) that activates immune cells, potentially enhancing its effectiveness against cancer. ^{1 2 3 4 7}

Research Team

Siddhartha Yadav, M.D.

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

Adults with invasive breast cancer that has spread (metastatic) and no curative standard therapy available. Must have good organ function, acceptable blood counts, ECOG status 0-2, and a life expectancy of at least 12 weeks. Cannot be pregnant or have had certain treatments recently.

Inclusion Criteria

I am taking medication for bone complications due to cancer and have tolerated it well.

I am able to care for myself and perform daily activities.

Willingness to return to the Mayo Clinic enrolling institution for follow-up

Exclusion Criteria

I need regular blood transfusions.

I have not had HER2 therapy in the last 3 weeks.

My cancer is causing or might soon cause serious problems by pressing on or invading into nearby organs.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive MV-s-NAP intratumorally on day 1. Cohort 1 receives a single treatment, while Cohort 2 receives treatment every 21 days for up to 3 cycles.

3-9 weeks

1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 3 months during year 1 and every 6 months during year 2.

Up to 2 years

Every 3 months in year 1, every 6 months in year 2 (in-person)

Treatment Details

Interventions

• Oncolytic Measles Virus Encoding Helicobacter pylori Neutrophil-activating Protein

Trial Overview The trial is testing MV-s-NAP, a modified measles virus designed to target and destroy breast cancer cells by producing an inflammatory protein called NAP. The study will determine the best dose and monitor its effects on metastatic breast cancer through various tests.

Participant Groups

Group I: Cohort 2 (multiple cycles MV-s-NAP) Experimental Treatment 4 Interventions

Patients receive MV-s-NAP IT on day 1 of each cycle. Cycles repeat every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI, tumor biopsy and blood sample collection throughout the study.

Group II: Cohort 1 (single treatment MV-s-NAP) Experimental Treatment 5 Interventions

Patients receive MV-s-NAP IT on day 1 in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI, tumor biopsy and blood sample collection throughout the study.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Engineered measles virus strains expressing Helicobacter pylori neutrophil-activating protein (NAP) effectively target and destroy metastatic breast cancer cells, leading to a significant increase in median survival (65 days vs. 29 days) in a pleural effusion xenograft model.

The therapeutic effect of these viruses is linked to a strong Th1 immune response, with increased levels of pro-inflammatory cytokines like TNF-α and IL-6, suggesting that combining oncolytic viruses with immunomodulators like NAP could enhance cancer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expression of immunomodulatory neutrophil-activating protein of Helicobacter pylori enhances the antitumor activity of oncolytic measles virus. Iankov, ID., Allen, C., Federspiel, MJ., et al.[2021]

The engineered measles virus (MV-s-NAP) demonstrated anti-tumor and immunostimulatory effects in breast cancer models, suggesting its potential as an effective treatment for metastatic breast cancer (MBC).

In a safety evaluation using a mouse model, both subcutaneous and intravenous delivery of MV-s-NAP showed no significant toxicity, supporting its safety for use in a planned phase I clinical trial for MBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical safety assessment of MV-s-NAP, a novel oncolytic measles virus strain armed with an H . pylori immunostimulatory bacterial transgene. Viker, KB., Steele, MB., Iankov, ID., et al.[2022]

The live attenuated measles virus vaccine effectively infected and destroyed breast cancer cells, particularly showing a strong cytotoxic effect on the AMJ13 cell line, with an IC50 of 3.527, compared to 5.079 for MCF-7 and 9.171 for CAL-51.

The measles virus treatment significantly induced apoptosis in the breast cancer cell lines, suggesting it could be a safe and promising anticancer therapy for breast cancer, especially in cases with functional BRCA1/BRCA2 genes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Attenuated measles vaccine strain have potent oncolytic activity against Iraqi patient derived breast cancer cell line. Abdullah, SA., Al-Shammari, AM., Lateef, SA.[2023]

Retargeted measles virus (MV) strains derived from the Edmonston vaccine lineage show promising potential as an oncolytic therapy for treating metastatic cancers, demonstrating comparable antitumor efficacy to unmodified strains.

These retargeted MV-Edm derivatives are engineered to bind specifically to tumor cells, which may enhance their therapeutic index and effectiveness in targeting cancerous tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncolytic measles virus retargeting by ligand display. Msaouel, P., Iankov, ID., Allen, C., et al.[2021]

The study demonstrated that an oncolytic measles virus modified to express human granulocyte colony-stimulating factor (MVhGCSF) can enhance the immune response against certain B-cell tumors, particularly in the Raji model, indicating its potential as a cancer treatment.

However, the effectiveness of MVhGCSF varies by tumor type, as it did not show the same enhancement in the Nalm-6 model, highlighting the need for tailored approaches in oncolytic virus therapies based on specific tumor characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Neutrophils in Measles Virus-mediated Oncolysis Differs Between B-cell Malignancies and Is Not Always Enhanced by GCSF. Dey, A., Zhang, Y., Castleton, AZ., et al.[2019]

Measles virus (MV) vaccine strains show strong potential as cancer treatments due to their ability to selectively target and kill tumor cells while sparing healthy cells.

These MV strains not only demonstrate significant preclinical effectiveness against various tumor models but also retain their oncolytic properties even when modified for specific targeting, making them a versatile option for cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic potential of oncolytic measles virus: promises and challenges. Galanis, E.[2010]

Intratumoral administration of low doses of the MMR vaccine (measles, mumps, and rubella) has shown promising results in controlling tumors and improving survival in mouse models of liver and colorectal cancer by enhancing the infiltration of effective immune cells like CD8+ T-cells.

The MMR vaccine activates both innate and adaptive immune responses against cancer, suggesting it could be a safe and cost-effective option for cancer immunotherapy, making it accessible to more patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repurposing live attenuated trivalent MMR vaccine as cost-effective cancer immunotherapy. Zhang, Y., Gabere, M., Taylor, MA., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Expression of immunomodulatory neutrophil-activating protein of Helicobacter pylori enhances the antitumor activity of oncolytic measles virus. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Preclinical safety assessment of MV-s-NAP, a novel oncolytic measles virus strain armed with an H . pylori immunostimulatory bacterial transgene. [2022]

3. Saudi Arabia pubmed.ncbi.nlm.nih.gov

Attenuated measles vaccine strain have potent oncolytic activity against Iraqi patient derived breast cancer cell line. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Oncolytic measles virus retargeting by ligand display. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

The Role of Neutrophils in Measles Virus-mediated Oncolysis Differs Between B-cell Malignancies and Is Not Always Enhanced by GCSF. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Therapeutic potential of oncolytic measles virus: promises and challenges. [2010]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Repurposing live attenuated trivalent MMR vaccine as cost-effective cancer immunotherapy. [2022]