TAA-specific CTLs for Breast Cancer

(TACTIC Trial)

Recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Baylor College of Medicine

Must not be taking: Systemic corticosteroids

Disqualifiers: Severe infection, HIV, Pregnancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 6-12 months

12 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop any investigational therapy for one month and any conventional therapy for at least one week before starting the study treatment. If you are on systemic corticosteroids, you must stop them at least 48 hours before participating.

What data supports the effectiveness of the treatment TAA-specific CTLs for breast cancer?

Research shows that TAA-specific CTLs (special immune cells that target cancer markers) have been used effectively in treating other cancers like multiple myeloma, non-Hodgkin lymphoma, and acute myeloid leukemia by targeting specific cancer markers. However, a study found that breast cancer patients did not show the same immune response to these markers, suggesting that the effectiveness might differ for breast cancer. ^{1 2 3 4 5}

Is TAA-specific CTL therapy safe for humans?

Research shows that TAA-specific CTL therapy has been tested in humans with various cancers, including breast cancer, and is considered potentially nontoxic, meaning it is generally safe. ^{1 2 5 6 7}

How is the TAA-specific CTLs treatment different from other breast cancer treatments?

TAA-specific CTLs treatment is unique because it uses the body's own immune cells, specifically cytotoxic T-lymphocytes, to target and destroy cancer cells by recognizing specific tumor-associated antigens, which is different from traditional treatments like chemotherapy that attack all rapidly dividing cells. ^{1 2 3 8 9}

What is the purpose of this trial?

Status - CLOSED TO PATIENT ENROLLMENT (CNPE) The study is being conducted in patients in which breast cancer has come back after standard treatment. Volunteers in this research study are treated using special immune system cells called tumor-associated antigen (TAA)-specific cytotoxic T lymphocytes, a new experimental therapy. The proteins that investigators are targeting in this study are called tumor-associated antigens (TAAs). These are cell proteins that are specific to the cancer cell. They do not show, or they show up in low quantities, on normal human cells. In this study, investigators target five common TAAs. They are called NY-ESO-1, MAGEA4, PRAME, Survivin and SSX2. On a different study, patients have been treated and so far this treatment has shown to be safe. Investigators now want to try this treatment in patients with breast cancer. These TAA-specific cytotoxic T lymphocytes (TAA-CTLs) are an investigational product not approved by the Food and Drug Administration. The purpose of this study is to determine the clinical efficacy of TAA-specific CTLs, to learn what the side-effects are, and to see whether this therapy might help patients with breast cancer.

Research Team

Mothaffar Rimawi, MD

Principal Investigator

Baylor College of Medicine

Anne Leen, PhD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

This trial is for adults aged 18-80 with breast cancer that has returned and is now metastatic or locally advanced and untreatable by surgery. They must have tried at least two treatments, have a life expectancy of 12+ weeks, stable organ function, no severe infections or uncontrolled conditions, not be on steroids or HIV positive, and agree to use effective birth control.

Inclusion Criteria

My breast cancer cannot be removed by surgery and has spread.

My breast cancer is spreading and treatments haven’t worked.

My kidney function, measured by creatinine, is normal for my age.

Exclusion Criteria

You have a serious ongoing infection.

I have not taken steroids for at least 48 hours.

You have a current HIV infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive TAA-specific cytotoxic T lymphocytes with initial two doses four weeks apart, followed by up to six additional doses if tumor reduction is observed

6-12 months

Multiple visits for infusions and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment, with blood tests and imaging studies

1 year

Regular visits for blood tests and imaging

Long-term follow-up

Annual contact for up to 4 additional years to evaluate disease response

4 years

Treatment Details

Interventions

• TAA-specific CTLs

Trial Overview The study tests TAA-specific cytotoxic T lymphocytes (TAA-CTLs), an experimental therapy targeting five common tumor-associated antigens (TAAs) in breast cancer cells. The goal is to evaluate the effectiveness and side effects of this new treatment in patients whose cancer has resisted standard therapies.

Participant Groups

Group I: TAA-Specific CTLs Experimental Treatment 1 Intervention

Patients receiving TAA-specific CTLs as therapy for breast cancer.

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Cancer Prevention Research Institute of Texas

Collaborator

Trials

55

Recruited

98,900+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials

114

Recruited

2,900+

The Methodist Hospital Research Institute

Collaborator

Trials

299

Recruited

82,500+

Findings from Research

Tumor-associated antigen-specific cytotoxic T lymphocytes (TAA-CTL) were safely generated and infused into patients with multiple myeloma and non-Hodgkin lymphoma, with no significant adverse reactions reported during the treatment.

In a small group of 7 patients, TAA-CTL therapy showed promising efficacy, as 5 patients experienced positive clinical effects, and an increase in specific immune responses was observed 2-3 weeks post-infusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Research of Dendritic Cell-Mediated Tumor-Associated Antigen-Specific Cytotoxic T Lymphocytes in the Treatment of Multiple Myeloma and Non-Hodgkin Lymphoma]. Li, XH., Xue, L., Xu, H., et al.[2020]

Cytotoxic T lymphocytes (CTLs) play a crucial role in fighting cancer by recognizing tumor-specific antigens, which are presented by cells in the body.

The review discusses the development of peptide-based vaccines that target these tumor-associated antigens, highlighting their potential to enhance the immune response against cancer and improve CTL therapy in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Tumor antigen-specific cytotoxic T lymphocytes and cancer immunotherapy - review]. Liu, Y.[2016]

In a study involving 9 patients with acute myeloid leukemia (AML) at high risk of relapse, the infusion of tumor-associated antigen-specific cytotoxic T lymphocytes (TAA-CTLs) showed promising safety, with no significant adverse reactions reported during or after treatment.

The TAA-CTL therapy demonstrated an antileukemic effect in 2 out of 5 patients who were minimal residual disease (MRD) positive, indicating potential efficacy in reducing leukemia without the need for additional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T cells targeting multiple tumor-associated antigens as a postremission treatment to prevent or delay relapse in acute myeloid leukemia. Xue, L., Hu, Y., Wang, J., et al.[2022]

In a first-in-human trial involving 15 patients with relapsed or refractory solid tumors, tumor-associated antigen cytotoxic T cells (TAA-Ts) were administered safely without any dose-limiting toxicities, demonstrating a promising new therapeutic approach.

Of the evaluable patients, 73% showed stable disease or better at day 45 post-infusion, with 6 patients remaining progression-free for a median of 13.9 months, indicating that TAA-Ts can effectively stabilize disease and prolong time to progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy of Relapsed and Refractory Solid Tumors With Ex Vivo Expanded Multi-Tumor Associated Antigen Specific Cytotoxic T Lymphocytes: A Phase I Study. Hont, AB., Cruz, CR., Ulrey, R., et al.[2020]

In a first-in-human trial involving 10 heavily pre-treated patients with relapsed or metastatic breast cancer, multi-antigen-targeted T cells (multiTAA-T) were well tolerated with no treatment-related toxicities, indicating a promising safety profile for this therapy.

One patient experienced prolonged disease stabilization for 5 months, which was linked to the in vivo expansion and persistence of T cells targeting specific tumor antigens, along with evidence of broader immune activation against non-targeted tumor antigens in 7 out of 10 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-antigen-targeted T-cell therapy to treat patients with relapsed/refractory breast cancer. Hoyos, V., Vasileiou, S., Kuvalekar, M., et al.[2022]

References

1. China pubmed.ncbi.nlm.nih.gov

[Clinical Research of Dendritic Cell-Mediated Tumor-Associated Antigen-Specific Cytotoxic T Lymphocytes in the Treatment of Multiple Myeloma and Non-Hodgkin Lymphoma]. [2020]

2. China pubmed.ncbi.nlm.nih.gov

[Tumor antigen-specific cytotoxic T lymphocytes and cancer immunotherapy - review]. [2016]

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

Differences in T-cell immunity toward tumor-associated antigens in colorectal cancer and breast cancer patients. [2016]

4. New Zealand pubmed.ncbi.nlm.nih.gov

T cells targeting multiple tumor-associated antigens as a postremission treatment to prevent or delay relapse in acute myeloid leukemia. [2022]

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

Immunotherapy of Relapsed and Refractory Solid Tumors With Ex Vivo Expanded Multi-Tumor Associated Antigen Specific Cytotoxic T Lymphocytes: A Phase I Study. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Identification of HLA-A2-restricted CTL epitopes of a novel tumour-associated antigen, KIF20A, overexpressed in pancreatic cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Multi-antigen-targeted T-cell therapy to treat patients with relapsed/refractory breast cancer. [2022]

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

Functional T cell responses to tumor antigens in breast cancer patients have a distinct phenotype and cytokine signature. [2020]

9. Germany pubmed.ncbi.nlm.nih.gov

[Determination of TAA-binding cells in peripheral blood of breast cancer patients (author's transl)]. [2006]