CAR T Cell Therapy for Breast Cancer

Overseen By Abramson Cancer Center Clinical Trials Service

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Pennsylvania

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Active cancer, Hepatitis, Autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

2 Participants Needed

Trial Summary

What is the purpose of this trial?

Phase 1 - Safety and Proof of Concept

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on high-dose corticosteroids or systemic immunosuppressive treatment, you may need to adjust your medication as per the trial's exclusion criteria.

What data supports the effectiveness of the treatment huCART-meso cells for breast cancer?

Research shows that meso-CAR-T cells, which target a protein called mesothelin found in breast cancer, can reduce tumor growth. Combining this treatment with another therapy called rAd.sT enhances its effectiveness, suggesting it could be a promising strategy for breast cancer. ^{1 2 3 4 5}

Is CAR T-cell therapy targeting mesothelin safe for humans?

CAR T-cell therapy targeting mesothelin has been generally well tolerated in humans, with one serious side effect (sepsis) reported in a study. Overall, it has shown a high safety profile, although its effectiveness in treating solid tumors is still being improved. ^{1 2 3 5 6}

What makes huCART-meso cells treatment unique for breast cancer?

The huCART-meso cells treatment is unique because it uses genetically engineered T-cells to specifically target and attack cancer cells by recognizing a protein called mesothelin, which is often found on the surface of breast cancer cells. This approach is different from traditional treatments like surgery or chemotherapy, as it aims to harness the body's immune system to fight the cancer. ^{3 5 7 8 9}

Research Team

Julia Tchou, MD, PhD

Principal Investigator

University of Pennsylvania

Eligibility Criteria

This trial is for adults over 18 with advanced triple-negative breast cancer that can't be removed by surgery or has spread, and whose tumors have a protein called mesothelin. They must be relatively healthy, not pregnant, and agree to use birth control. People with autoimmune diseases needing strong meds, other cancers, hepatitis B or C, serious infections or heart/lung problems can't join.

Inclusion Criteria

I am fully active or can carry out light work.

My organs and bone marrow are working well.

My breast cancer is advanced, cannot be surgically removed, and lacks certain hormone receptors and HER2.

Exclusion Criteria

I currently have an infection.

I do not have serious heart problems that could interfere with the study.

I am taking strong medication for an autoimmune disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intratumoral injections of CAR T cells at different dose levels

6 weeks

Weekly visits for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Bi-weekly visits for monitoring

Treatment Details

Interventions

• huCART-meso cells

Trial Overview The study is testing the safety of a new therapy using CAR T cells (huCART-meso cells) designed to target mesothelin in breast cancer. It's an early-phase trial to see if this approach could work as a treatment. Participants will also undergo tests to confirm their tumor expresses mesothelin.

Participant Groups

Group I: Dose Level 1 Experimental Treatment 2 Interventions

3.00 x 10\^7 CAR T cells administered intratumoral

Group II: Dose Level -1 Experimental Treatment 2 Interventions

3.00 x 10\^6 CAR T cells administered intratumoral

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Findings from Research

The study involved 15 patients with chemotherapy-refractory cancers, and the lentiviral-transduced CAR T cells targeting mesothelin (CART-meso) were generally well tolerated, with only one case of severe toxicity (sepsis) reported.

While CART-meso cells expanded in the blood and were detectable in tumor biopsies, the overall clinical response was limited, with the best outcome being stable disease in 11 out of 15 patients, indicating the need for further research into more effective CAR designs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of Lentiviral-Transduced Chimeric Antigen Receptor-Modified T Cells Recognizing Mesothelin in Advanced Solid Cancers. Haas, AR., Tanyi, JL., O'Hara, MH., et al.[2023]

Meso3 CAR T cells, targeting the membrane-proximal region of mesothelin, showed superior activation and cytokine production compared to meso1 CAR T cells, indicating a more effective immune response against cancer cells.

In animal models, meso3 CAR T cells demonstrated stronger antitumor effects in gastric and ovarian cancers, suggesting that this approach could be a more effective immunotherapy for treating mesothelin-positive solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified CAR T cells targeting membrane-proximal epitope of mesothelin enhances the antitumor function against large solid tumor. Zhang, Z., Jiang, D., Yang, H., et al.[2021]

CAR T-cell therapy has shown promising results in treating hematologic malignancies and is being explored as a potential treatment for breast cancer, which remains a leading cause of cancer death among women.

Preclinical studies indicate that CAR T-cells can enhance anti-breast cancer activity both in laboratory settings and in living organisms, suggesting they may be an effective therapeutic option for breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New approaches in chimeric antigen receptor T-cell therapy for breast cancer. Zhang, Q., Ding, B., Qian, L., et al.[2020]

The combination of meso-CAR-T cells, which target mesothelin in breast cancer, with the oncolytic adenovirus rAd.sT significantly enhances antitumor responses compared to either treatment alone, as shown in a study using MDA-MB-231 xenograft models in mice.

This combination therapy not only reduces tumor growth more effectively but also boosts the production of important cytokines like IL-6 and IL-12 in the tumor microenvironment, suggesting a synergistic effect that could improve treatment outcomes for breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncolytic adenovirus targeting TGF-β enhances anti-tumor responses of mesothelin-targeted chimeric antigen receptor T cell therapy against breast cancer. Li, Y., Xiao, F., Zhang, A., et al.[2021]

Anti-MSLN CAR-T-cell therapy has demonstrated a high safety profile in clinical trials, making it a promising option for treating solid tumors, although its efficacy remains limited.

Combining anti-MSLN CAR-T-cell therapy with standard treatments has shown significantly better outcomes than using the therapy alone, suggesting that combination strategies may enhance its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenges of Anti-Mesothelin CAR-T-Cell Therapy. Zhai, X., Mao, L., Wu, M., et al.[2023]

HER2 CAR T-cell therapy shows promise for treating solid tumors, particularly in cancers like breast cancer, but it carries significant risks of severe side effects, such as cytokine release syndrome due to targeting HER2 on non-cancerous tissues.

The review highlights ongoing efforts to enhance the safety of HER2 CAR therapies through novel designs and alternative CAR host selections, aiming to minimize the risk of toxicities while maintaining therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Driving better and safer HER2-specific CARs for cancer therapy. Liu, X., Zhang, N., Shi, H.[2019]

Immunotherapy, particularly CAR-T therapy, is emerging as a promising treatment for breast cancer, which remains a leading cause of cancer-related deaths among women.

While CAR-T therapy has shown success in treating blood cancers, challenges exist in applying it to solid tumors like breast cancer; ongoing research aims to enhance its effectiveness and manage potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Approaches in CAR-T Cell Immunotherapy for Breast Cancer. Wang, J., Zhou, P.[2018]

CAR T-cell therapy has shown great promise in treating blood cancers but faces significant challenges when applied to solid tumors, such as breast cancer, due to issues like poor T cell trafficking and an immunosuppressive tumor environment.

Current research is focused on developing strategies to improve the effectiveness of CAR T-cells in solid tumors, aiming to overcome the limitations that have hindered their success in these types of cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor-T cells immunotherapy for targeting breast cancer. Rahimmanesh, I., Khanahmad, H.[2021]

Chimeric antigen receptor (CAR)-T cell therapy shows promise for treating metastatic breast cancer, but its effectiveness is limited by challenges such as the complex tumor microenvironment and the lack of ideal tumor antigens.

Potential targets for CAR-T therapy in breast cancer include HER-2, C-MET, and EGFR, and the paper discusses strategies to overcome issues like off-target effects and heterogeneous antigen expression to enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current progress in chimeric antigen receptor-modified T cells for the treatment of metastatic breast cancer. Yin, L., Chen, GL., Xiang, Z., et al.[2023]

References

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

Phase I Study of Lentiviral-Transduced Chimeric Antigen Receptor-Modified T Cells Recognizing Mesothelin in Advanced Solid Cancers. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Modified CAR T cells targeting membrane-proximal epitope of mesothelin enhances the antitumor function against large solid tumor. [2021]

3. China pubmed.ncbi.nlm.nih.gov

New approaches in chimeric antigen receptor T-cell therapy for breast cancer. [2020]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Oncolytic adenovirus targeting TGF-β enhances anti-tumor responses of mesothelin-targeted chimeric antigen receptor T cell therapy against breast cancer. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Challenges of Anti-Mesothelin CAR-T-Cell Therapy. [2023]

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

Driving better and safer HER2-specific CARs for cancer therapy. [2019]

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

New Approaches in CAR-T Cell Immunotherapy for Breast Cancer. [2018]

8. Iran pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor-T cells immunotherapy for targeting breast cancer. [2021]

9. France pubmed.ncbi.nlm.nih.gov

Current progress in chimeric antigen receptor-modified T cells for the treatment of metastatic breast cancer. [2023]