MUC1-Activated T Cells for Ovarian Cancer

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Mayo Clinic

Must not be taking: Steroids, Antiretrovirals, Investigational agents, others

Disqualifiers: CNS metastases, Plasma cell leukemia, others

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

Compensation: Varies

Number of Visits: 31

Duration: 4 weeks

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of using modified T cells to combat ovarian cancer that has recurred or resisted treatment. Researchers extract T cells from the patient, alter them in a lab to target a specific protein (MUC1) on cancer cells, and then return them to the patient to help destroy the cancer. This method is known as Autologous MUC1-activated T-cells or MUC1-targeted T-cell therapy. Patients with relapsed or treatment-resistant ovarian cancer, who have a confirmed diagnosis and measurable disease, may be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this innovative therapy.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, if you are on certain treatments like high-dose steroids or other investigational agents, you may not be eligible to participate.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that MUC1-activated T cells are undergoing safety testing for ovarian cancer treatment. Technicians take these T cells from the patient, modify them in a lab to target the MUC1 protein on cancer cells, and then return them to the patient.

As this is an early-stage study, the main goal is to assess patient tolerance and determine the optimal dose. Similar treatments have caused some side effects, but these are usually manageable. The study will closely monitor any side effects to ensure maximum safety.

While data on MUC1-activated T cells remains limited, similar treatments have shown promise in enhancing the immune system's ability to fight cancer. This trial aims to gather solid safety data to build on that promise. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ovarian cancer?

Researchers are excited about MUC1-activated T cells for ovarian cancer because these cells offer a personalized approach by using the patient's own immune cells. Unlike traditional treatments such as chemotherapy or surgery, which can affect healthy cells, this method involves modifying T cells to specifically target cancer cells expressing the MUC1 protein. This targeted action could potentially lead to fewer side effects and a more effective attack on the cancer. Additionally, the use of immune cells activated to recognize and fight cancer offers a new mechanism of action, setting it apart from existing therapies.

What evidence suggests that MUC1-activated T cells might be an effective treatment for ovarian cancer?

Research has shown that specially modified immune cells, called MUC1-activated T cells, have potential in treating ovarian cancer. In this trial, participants will receive MUC1-activated T cells, designed to target a protein called MUC1 found on many cancer cells, helping the immune system recognize and attack the tumor. Early findings suggest that this method can strengthen the immune response and may improve outcomes for patients with advanced ovarian cancer. Specifically, studies have found that patients receiving this treatment experienced better therapeutic effects, indicating its potential effectiveness. Initial research also notes that these MUC1-specific T cells can change immune cell populations in a way that may benefit cancer therapy. ^{1 2 3 6 7}

Who Is on the Research Team?

Brenda J Ernst, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for patients with ovarian cancer that has returned or resisted treatment. Participants must have a specific protein, MUC1, on their tumor cells. They will undergo various imaging tests and procedures like leukapheresis to prepare T-cells.

Inclusion Criteria

My ovarian cancer cells test positive for MUC1.

Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) criteria on study entry

Provide written informed consent

Exclusion Criteria

Patients receiving any other investigational agent which could be considered a treatment for the neoplasm

I have been diagnosed with another cancer within the last 4 years.

I have untreated or ongoing brain metastases.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Leukapheresis and Lymphodepletion

Patients undergo leukapheresis and receive cyclophosphamide or bendamustine for lymphodepletion

1 week

Multiple visits (in-person)

Treatment

Patients receive MUC1-activated T cells intravenously and undergo various imaging and blood sample collections

4 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Visits at 30 and 60 days from day 28, then every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Autologous MUC1-activated T-cells

Trial Overview The trial is testing the safety and optimal dosage of lab-made MUC1-activated T cells in treating relapsed/resistant ovarian cancer. These are patient's own immune cells modified to target and kill cancer cells expressing the MUC1 protein.

How Is the Trial Designed?

Group I: Treatment (MUC1-activated T cells, lymphodepletion) Experimental Treatment 10 Interventions

Patients undergo leukapheresis over 4 hours within 14 days after registration. Patients receive cyclophosphamide IV over 60 minutes on days -5 to -3 or bendamustine IV over 10 minutes on days -5 and -4 or -4 and -3. Patients receive MUC1-activated T cells IV over 10-60 minutes on day 0 or days 0 and 21. Patients also undergo ECHO or MUGA during screening, and blood sample collection throughout the trial. In addition, patients may undergo CT, MRI, or PET/CT as clinically indicated throughout the trial. Patients may also undergo collection of ascites on study and during follow up.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

In a new tumor model for ovarian cancer using MUC1-expressing cells, anti-PD-L1 antibody treatment significantly increased T cell infiltration and improved survival rates in mice, indicating its potential efficacy in advanced ovarian cancer.

The study found that earlier treatment and more frequent doses of anti-PD-L1 were necessary to enhance T cell responses and prolong survival, suggesting that timing and dosage are critical factors for optimizing immune checkpoint blockade therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-PD-L1 prolongs survival and triggers T cell but not humoral anti-tumor immune responses in a human MUC1-expressing preclinical ovarian cancer model. Mony, JT., Zhang, L., Ma, T., et al.[2018]

Adoptive cell therapy using human interleukin 2-activated large granular lymphocytes and T-cells significantly extended the survival of nude mice with ovarian cancer, with mean survival times increasing from 30 to 60 days.

Monocytes, even when activated with gamma-interferon, did not improve survival, suggesting that not all immune cell types are equally effective in this therapeutic approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive cellular immunotherapy of human ovarian carcinoma xenografts in nude mice. Ortaldo, JR., Porter, HR., Miller, P., et al.[2003]

Adoptive T cell immunotherapy using autologous MUC1 peptide-stimulated CD4(+) effector cells in ovarian cancer patients showed promising results, with some patients experiencing diminished tumor markers and enhanced survival rates after three treatment cycles.

Long-term survivors exhibited increased levels of specific T cell populations that correlated with better outcomes, suggesting that the balance of regulatory T cells may play a crucial role in sustaining tumor immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous MUC1-specific Th1 effector cell immunotherapy induces differential levels of systemic TReg cell subpopulations that result in increased ovarian cancer patient survival. Dobrzanski, MJ., Rewers-Felkins, KA., Quinlin, IS., et al.[2021]

In a study involving 22 patients with advanced cancers, treatment with activated autologous lymphocytes showed no evidence of inducing autoimmune disease, as most patients maintained normal levels of autoimmune markers throughout the treatment.

While mild transient fever was noted as an adverse event, no significant autoimmune symptoms were observed, suggesting that this therapy is relatively safe in terms of autoimmune side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term intravenous administration of activated autologous lymphocytes for cancer patients does not induce antinuclear antibody and rheumatoid factor. Yamaguchi, T., Bamba, K., Kitayama, A., et al.[2017]

Immunization of MUC1.Tg mice with human MUC1 antigen led to the production of anti-MUC1 antibodies but did not trigger a cytotoxic T cell response, indicating a potential limitation in the immune response against MUC1-associated tumors.

The study found that immunization resulted in decreased levels of CD8+ T cells and down-regulation of T cell receptors, suggesting that tolerance to the MUC1 antigen may involve T cell suppression in these mice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T cell suppression as a mechanism for tolerance to MUC1 antigen in MUC1 transgenic mice. Chen, D., Koido, S., Li, Y., et al.[2019]

MUC1 is overexpressed in more than 90% of advanced epithelial ovarian cancers (EOCs) and their metastatic lesions, while it is rarely found in normal ovarian tissues, indicating its potential as a tumor marker.

The high levels of MUC1 expression are significantly associated with worse progression parameters of EOC, such as tumor stage and presence of ascites, suggesting that targeting MUC1 could be a promising strategy for treating recurrent metastatic EOC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expression of MUC1 in primary and metastatic human epithelial ovarian cancer and its therapeutic significance. Wang, L., Ma, J., Liu, F., et al.[2022]

A specific population of tissue-resident memory T cells (TIM-3/CXCL13-positive) was identified in epithelial ovarian cancer (EOC), which is associated with improved survival in patients, based on analysis of around 175 patients with high-grade serous EOC.

The study suggests that combining TIM-3 and PD-1 blockade therapies could enhance anti-cancer immunity in EOC, particularly since CXCL13-positive CD8 T cells are linked to better responses to existing immunotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor infiltrating CD8/CD103/TIM-3-expressing lymphocytes in epithelial ovarian cancer co-express CXCL13 and associate with improved survival. Vlaming, M., Bilemjian, V., Freile, JÁ., et al.[2022]

In a phase I/II study involving patients with recurrent ovarian cancer, adoptive T cell therapy using IL-10- and IFN-γ-producing CD4 effector cells showed promising results, with some patients experiencing prolonged survival and one remaining disease-free after treatment.

The study found that the effectiveness of the therapy was linked to specific ratios of TReg cell subpopulations rather than their overall numbers, suggesting that the balance of these immune cells plays a crucial role in enhancing long-term tumor immunity and T cell memory.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy with IL-10- and IFN-γ-producing CD4 effector cells modulate "Natural" and "Inducible" CD4 TReg cell subpopulation levels: observations in four cases of patients with ovarian cancer. Dobrzanski, MJ., Rewers-Felkins, KA., Samad, KA., et al.[2021]

In a study involving six multiple myeloma patients, cytotoxic T lymphocyte (CTL) lines were successfully induced from two patients, demonstrating the potential to target MUC1, a tumor-associated antigen, in myeloma and breast carcinoma cells.

The CTL lines showed effective cytotoxicity against MUC1+ cancer cells, and their activity was specifically inhibited by antibodies targeting MUC1, indicating that these CTLs can recognize and attack cancer cells expressing this antigen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytotoxic T lymphocytes derived from bone marrow mononuclear cells of multiple myeloma patients recognize an underglycosylated form of MUC1 mucin. Noto, H., Takahashi, T., Makiguchi, Y., et al.[2019]

MUC1 glycoprotein is frequently overexpressed in various cancers, making it a promising target for antitumor immunotherapy, with T-cell responses observed in both HLA-restricted and unrestricted manners.

Encouraging results from phase II/III clinical trials of MUC1-based vaccines indicate their potential effectiveness in inducing specific cytotoxic T cell responses against tumors, although some animal studies suggest the need to monitor for tolerogenic responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MUC1-specific cytotoxic T lymphocytes in cancer therapy: induction and challenge. Roulois, D., Grégoire, M., Fonteneau, JF.[2021]

A new preclinical mouse model for MUC1-positive ovarian tumors was developed, which closely mimics human ovarian cancer, showing increased metastasis and immune suppression, making it a valuable tool for testing therapies.

Vaccination with dendritic cells loaded with a MUC1 peptide effectively activates the immune response and prolongs survival in these mice, highlighting MUC1 as a promising target for immune-based treatments in ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunobiology of human mucin 1 in a preclinical ovarian tumor model. Budiu, RA., Elishaev, E., Brozick, J., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06483048

Study Details | NCT06483048 | MUC1-Activated T Cells for ... This phase I trial tests the safety, side effects, best dose of MUC1-activated T cells in treating patients with ovarian cancer that has come back after a ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-05158

MUC1-Activated T Cells for the Treatment of Relapsed and ... This phase I trial tests the safety, side effects, best dose of MUC1-activated T cells in treating patients with ovarian cancer that has come back after a ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2805085/

Autologous MUC1-Specific Th1 Effector Cell ... Adoptively transferred autologous MUC1-stimulated CD4 effector T cells enhance therapeutic efficacy among ovarian cancer patients with late stage disease.

4. mayo.edu mayo.edu/research/clinical-trials/cls-20569430

Clinical Trials The purpose of this study determine the toxicity of in-house, manufactured MUC1-activated T cells in patients with relapsed/refractory MUC1-expressing ovarian ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1521661609007712

Autologous MUC1-specific Th1 effector cell ... Autologous MUC1-specific Th1 effector cell immunotherapy induces differential levels of systemic TReg cell subpopulations that result in increased ovarian ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11049291/

CAR-T Cell Therapy in Ovarian Cancer: Where Are We Now? Several early phase clinical trials are currently evaluating CAR-T cell therapies targeting mesothelin, folate receptor a, HER2, MUC16, and B7H3.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0090825824001860

Adoptive T cell therapy for ovarian cancer A process called adoptive cell therapy (ACT), is a promising therapeutic option for the treatment of ovarian cancer.