Measles Virus-Based Vaccine for Breast Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Mayo Clinic
Must not be taking: Corticosteroids, others
Disqualifiers: Active infection, Heart disease, CNS metastases, HIV, others
No Placebo Group
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.
12345Is 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.
12356How 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.
12347Eligibility 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
+14 more
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.
+20 more
Trial 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)
Participant Groups
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.
2Treatment groups
Experimental Treatment
Group I: Cohort 2 (multiple cycles MV-s-NAP)Experimental Treatment4 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 Treatment5 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Mayo Clinic in RochesterRochester, MN
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Who Is Running the Clinical Trial?
Mayo ClinicLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Expression of immunomodulatory neutrophil-activating protein of Helicobacter pylori enhances the antitumor activity of oncolytic measles virus. [2021]Helicobacter pylori neutrophil-activating protein (NAP) is a major virulence factor and powerful inducer of inflammatory reaction and Th1-polarized immune response. Here, we evaluated the therapeutic efficacy of measles virus (MV) strains engineered to express secretory NAP forms against metastatic breast cancer. Recombinant viruses encoding secretory NAP forms (MV-lambda-NAP and MV-s-NAP) efficiently infect and destroy breast cancer cells by cell-to-cell viral spread and large syncytia formation independently of hormone receptor status. Intrapleural administration of MV-s-NAP doubled the median survival in a pleural effusion xenograft model: 65 days as compared to 29 days in the control group (P
Preclinical safety assessment of MV-s-NAP, a novel oncolytic measles virus strain armed with an H . pylori immunostimulatory bacterial transgene. [2022]Despite recent therapeutic advances, metastatic breast cancer (MBC) remains incurable. Engineered measles virus (MV) constructs based on the attenuated MV Edmonston vaccine platform have demonstrated significant oncolytic activity against solid tumors. The Helicobacter pylori neutrophil-activating protein (NAP) is responsible for the robust inflammatory reaction in gastroduodenal mucosa during bacterial infection. NAP attracts and activates immune cells at the site of infection, inducing expression of pro-inflammatory mediators. We engineered an MV strain to express the secretory form of NAP (MV-s-NAP) and showed that it exhibits anti-tumor and immunostimulatory activity in human breast cancer xenograft models. In this study, we utilized a measles-infection-permissive mouse model (transgenic IFNAR KO-CD46Ge) to evaluate the biodistribution and safety of MV-s-NAP. The primary objective was to identify potential toxic side effects and confirm the safety of the proposed clinical doses of MV-s-NAP prior to a phase I clinical trial of intratumoral administration of MV-s-NAP in patients with MBC. Both subcutaneous delivery (corresponding to the clinical trial intratumoral administration route) and intravenous (worst case scenario) delivery of MV-s-NAP were well tolerated: no significant clinical, laboratory or histologic toxicity was observed. This outcome supports the safety of MV-s-NAP for oncolytic virotherapy of MBC. The first-in-human clinical trial of MV-s-NAP in patients with MBC (ClinicalTrials.gov: NCT04521764) was subsequently activated.
Attenuated measles vaccine strain have potent oncolytic activity against Iraqi patient derived breast cancer cell line. [2023]One of the world's leading causes of death among females is breast cancer. Oncolytic viruses are promising anticancer therapy that can overcome resistance to current conventional therapies. Measles virus replicates in and destroys malignant cells without affecting healthy cells. The study aimed to evaluate the lives attenuated Measles virus vaccine against Iraqi patient derived breast cancer cells that have functional BRCA1/BRCA2 genes and compare its activity against international breast cancer MCF-7 and CAL-51 cell lines.
Oncolytic measles virus retargeting by ligand display. [2021]Despite significant advances in recent years, treatment of metastatic malignancies remains a significant challenge. There is an urgent need for development of novel therapeutic approaches. Virotherapy approaches have considerable potential, and among them measles virus (MV) vaccine strains have emerged as a promising oncolytic platform. Retargeted MV strains deriving from the Edmonston vaccine lineage (MV-Edm) have shown comparable antitumor efficacy to unmodified strains against receptor expressing tumor cells with improved therapeutic index. Here, we describe the construction, rescue, amplification, and titration of fully retargeted MV-Edm derivatives displaying tumor specific receptor binding ligands on the viral surface in combination with H protein CD46 and SLAM entry ablating mutations.
The Role of Neutrophils in Measles Virus-mediated Oncolysis Differs Between B-cell Malignancies and Is Not Always Enhanced by GCSF. [2019]The mechanism by which oncolytic measles virus (MV) kills cancer cells remains obscure. We previously showed that neutrophils are involved in MV-mediated tumor regressions and become activated, upon MV infection. In the present study, we attempted to enhance the neutrophil response toward MV-infected tumor targets by generating an oncolytic MV-expressing human granulocyte colony-stimulating factor (MVhGCSF). Evaluating the effects in two different models of B-cell malignancy, we showed that depletion of neutrophils abrogated the MV therapeutic effect in an in vivo Raji-but not Nalm-6 tumor model. Next, we compared MVhGCSF with the unmodified backbone virus MVNSe. MVhGCSF enhanced the oncolytic capacity of MV in the Raji model in vivo, whereas in the Nalm-6 model, the opposite was unexpectedly the case. This finding was recapitulated by exogenously administered hGCSF. MVhGCSF replicated within an MV-infectable CD46 transgenic mouse model with detectable serum levels of hGCSF but no toxicity. Our data suggest that a "one-size-fits-all" model of immune response to viral oncolysis is not appropriate, and each tumor target will need full characterization for the potential of both direct and indirect, innate immune responses to generate benefit.
Therapeutic potential of oncolytic measles virus: promises and challenges. [2010]Measles virus (MV) is a negative-strand RNA virus (paramyxovirus) with oncolytic properties. The significant preclinical activity of MV vaccine strains against a variety of tumor models, their potent bystander effect, their selectivity against tumor cells, and their ability to retain their oncolytic properties when engineered and retargeted makes them a promising oncolytic platform. In this article, we review potential applications and challenges associated with use of MV strains as cancer therapeutics.
Repurposing live attenuated trivalent MMR vaccine as cost-effective cancer immunotherapy. [2022]It has long been known that oncolytic viruses wield their therapeutic capability by priming an inflammatory state within the tumor and activating the tumor immune microenvironment, resulting in a multifaceted antitumor immune response. Vaccine-derived viruses, such as measles and mumps, have demonstrated promising potential for treating human cancer in animal models and clinical trials. However, the extensive cost of manufacturing current oncolytic viral products makes them far out of reach for most patients. Here by analyzing the impact of intratumoral (IT) administrations of the trivalent live attenuated measles, mumps, and rubella viruses (MMR) vaccine, we unveil the cellular and molecular basis of MMR-induced anti-cancer activity. Strikingly, we found that IT delivery of low doses of MMR correlates with tumor control and improved survival in murine hepatocellular cancer and colorectal cancer models via increased tumor infiltration of CD8+ granzyme B+ T-cells and decreased macrophages. Moreover, our data indicate that MMR activates key cellular effectors of the host's innate and adaptive antitumor immunity, culminating in an immunologically coordinated cancer cell death. These findings warrant further work on the potential for MMR to be repurposed as safe and cost-effective cancer immunotherapy to impact cancer patients globally.