Modified Immune Cells for Prostate Cancer

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must be taking: Zoledronic acid

Must not be taking: Checkpoint inhibitors

Disqualifiers: Hepatitis, HIV, Heart disease, others

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

Compensation: Varies

Number of Visits: Unknown

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase 1 single center clinical trial for patients with end stage Metastatic Castration Resistant Prostate Cancer who have progressed through standard of care treatment options and are on zoledronate for bone metastases. This clinical trial includes a dose-escalation phase and dose-expansion phase to assess the safety and preliminary efficacy of treatment with autologous T cells genetically modified to express Prostate stem cell antigen.

Will I have to stop taking my current medications?

The trial requires that you stop any anticancer therapy, including chemotherapy, biologic therapy, radiation, or immunotherapy, at least 3 weeks before the T cell infusion. If you are on zoledronic acid or denosumab, specific instructions are provided for switching or continuing these medications.

What data supports the effectiveness of this treatment for prostate cancer?

Research suggests that targeting prostate cancer cells with genetically engineered T-cells that recognize the prostate stem cell antigen (PSCA) is a promising strategy, as PSCA is widely present on prostate cancer cells. Additionally, CAR T-cell therapy, which involves modifying T-cells to better attack cancer cells, has shown potential in treating prostate cancer by targeting specific antigens like PSMA, although challenges remain with solid tumors. ^{1 2 3 4 5}

Is the treatment with modified immune cells for prostate cancer generally safe in humans?

The research on modified immune cells for prostate cancer, such as CAR-engineered NK-92 cells, includes safety measures like lethal irradiation to prevent replication, which did not affect their short-term function. This suggests a focus on safety, but specific human safety data is not detailed in the provided studies. ^{1 3 5 6 7}

What makes the treatment MSGV1-PSCA-8T28Z unique for prostate cancer?

MSGV1-PSCA-8T28Z is unique because it uses genetically modified immune cells, specifically gamma delta T cells, to target the prostate stem cell antigen (PSCA) on cancer cells, which is a novel approach compared to traditional treatments. This method aims to enhance the immune system's ability to specifically attack prostate cancer cells, offering a new strategy for treating advanced stages of the disease. ^{1 2 3 5 6}

Research Team

Jingsong Zhang, MD

Principal Investigator

Moffitt Cancer Center

Daniel Abate-Daga, PhD

Principal Investigator

Moffitt Cancer Center

Eligibility Criteria

This trial is for individuals with advanced prostate cancer that has spread and resisted treatment, who are currently on zoledronate for bone metastases. It's designed to find out if a new therapy using the patient's own modified T cells can safely target cancer cells.

Inclusion Criteria

Patients who are eligible for this study will not have childbearing potential, any patient deemed to have child fathering potential must agree to use adequate contraception from the time of screening to at least 6 months after administration of gamma delta enriched T cell infusion

I have had 2 chemotherapy treatments and 1 hormone therapy for my cancer.

I received my last zoledronic acid dose more than 4 weeks ago and need a booster before starting lymphodepletion chemotherapy.

Exclusion Criteria

I have had pancreatitis before.

I might have untreated cancer spread to my brain.

I have cancer spread to my brain or its surrounding areas.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants undergo leukapheresis followed by lymphodepletion and infusion of MSGV1-PSCA-8T28Z. The standard '3+3' design is used to guide dose escalation/de-escalation decisions.

3 days for lymphodepletion, followed by infusion

Dose Expansion

Participants receive MSGV1-PSCA-8T28Z at the Maximum Tolerated Dose determined in the dose escalation phase.

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of circulating tumor cell count and radiographic progression-free survival.

Up to 5 years

Treatment Details

Interventions

• Cyclophosphamide
• Fludarabine
• MSGV1-PSCA-8T28Z

Trial Overview The study tests autologous T cells (the patient's own immune cells) that have been genetically altered to attack prostate cancer by targeting Prostate Stem Cell Antigen. The trial includes initial phases to determine safe dosage levels and later phases to evaluate how well these modified T cells work.

Participant Groups

Group I: Dose Expansion Experimental Treatment 3 Interventions

Participants will undergo leukapheresis followed by lymphodepletion and infusion of MSGV1-PSCA-8T28Z. Lymphodepletion will include 3 days of treatment with fludarabine (30 mg/m\^2) and cyclophosphamide (500 mg/m\^2) prior to study day 0. Participants will then receive MSGV1-PSCA-8T28Z at the dose level determined to be the Maximum Tolerated Dose (MTD) in the dose escalation portion of the study.

Group II: Dose Escalation Experimental Treatment 3 Interventions

Participants will undergo leukapheresis followed by lymphodepletion and infusion of MSGV1-PSCA-8T28Z. The lymphodepletion regimen includes cyclophosphamide (500 mg/m2) and fludarabine (30 mg/m2) administered over 3 days (Days -5, -4, -3). The standard "3+3" design will be used to guide dose escalation/de-escalation decisions based on the cumulative number of patients who experience a dose limiting toxicity (DLT) at the current dose. The first cohort of 3 patients will be treated at dose level 1. The target maximum doses infused at each dose level is: Dose Level 1: 1x10\^5 cells/kg Dose Level 2: 3x10\^5 cells/kg Dose Level 3: 1x10\^6 cells/kg Dose Level 4: 3x10\^6 cells/kg Dose Level 5: 1x10\^6 cells/kg

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Findings from Research

Prostate cancer cells that form spheres (prostaspheres) show resistance to destruction by γδ T cells and have higher levels of stemness markers, indicating a link between cancer stem cells and treatment resistance.

Ex vivo-expanded γδ T cells are ineffective against prostate cancer stem cells, suggesting that targeting these stem cells may be crucial for improving immunotherapy outcomes in recurrent and metastatic prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sphere-derived Prostate Cancer Stem Cells Are Resistant to γδ T Cell Cytotoxicity. Miyashita, M., Tomogane, M., Nakamura, Y., et al.[2020]

A new chimeric T-cell receptor (TCR) targeting the prostate stem cell antigen (PSCA) was successfully developed, showing promise for treating prostate cancer by activating cytotoxic T-cells against PSCA-positive tumor cells.

This innovative approach involves genetic engineering of T-cells to enhance their ability to recognize and attack prostate cancer cells, potentially offering a new immunotherapeutic strategy for patients with minimal residual disease or advanced tumor stages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting of tumor cells expressing the prostate stem cell antigen (PSCA) using genetically engineered T-cells. Morgenroth, A., Cartellieri, M., Schmitz, M., et al.[2021]

In a study of 43 patients undergoing prostate biopsy, the distribution of gamma-delta (γδ) T cells in blood and prostate tissue showed no significant differences between those with and without prostate cancer, indicating that these immune cells may not be reliable biomarkers for cancer diagnosis.

There was a non-significant trend suggesting that higher-grade prostate cancer (ISUP grade ≥2) may have lower levels of γδ T cell infiltration, hinting at a potential role for these cells in the immune response against prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of human infiltrating and circulating gamma-delta T cells in prostate cancer. Vella, M., Coniglio, D., Abrate, A., et al.[2020]

The study demonstrates that PSMA-targeting CAR T cells, which are engineered to include a dominant-negative TGFβ receptor, are safe and feasible for use in treating prostate cancer.

This approach suggests a promising strategy for enhancing the effectiveness of CAR T cell therapy in prostate cancer patients, potentially improving their treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T Cells with a Dominant-Negative TGFβ Receptor Are Safe and Feasible. [2022]

Engineering NK-92 cells with a CAR that targets the prostate-specific membrane antigen (PSMA) allows these cells to effectively kill prostate cancer cells while sparing healthy cells, demonstrating strong potential for targeted therapy.

In mouse models, irradiated NK-92/CAR cells not only inhibited tumor growth but also improved survival rates, suggesting that this approach could be a promising and safe immunotherapy for advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-PSMA CAR-engineered NK-92 Cells: An Off-the-shelf Cell Therapy for Prostate Cancer. Montagner, IM., Penna, A., Fracasso, G., et al.[2021]

The study developed a third-generation CAR T cell targeting the prostate stem cell antigen (PSCA), which showed specific immune responses and effective tumor cell killing in laboratory tests.

In mouse models, treatment with PSCA-CAR T cells significantly delayed tumor growth and improved survival, suggesting potential for this therapy in treating prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic treatment with CAR-engineered T cells against PSCA delays subcutaneous tumor growth and prolongs survival of mice. Hillerdal, V., Ramachandran, M., Leja, J., et al.[2021]

The dendritic cell-directed lentiviral vector (DCLV) encoding murine PSCA (DCLV-PSCA) effectively delivered the PSCA antigen to immune cells, leading to a strong immune response with CD8(+) and CD4(+) T cells in mouse models.

In mouse models of prostate cancer, DCLV-PSCA vaccination provided significant protection against tumor growth and metastasis, indicating its potential as a powerful immunotherapy for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dendritic cell-directed vaccination with a lentivector encoding PSCA for prostate cancer in mice. Xiao, L., Joo, KI., Lim, M., et al.[2022]

References

1. Greece pubmed.ncbi.nlm.nih.gov

Sphere-derived Prostate Cancer Stem Cells Are Resistant to γδ T Cell Cytotoxicity. [2020]

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

Targeting of tumor cells expressing the prostate stem cell antigen (PSCA) using genetically engineered T-cells. [2021]

3. Korea (South) pubmed.ncbi.nlm.nih.gov

Characterization of human infiltrating and circulating gamma-delta T cells in prostate cancer. [2020]

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

CAR T Cells with a Dominant-Negative TGFβ Receptor Are Safe and Feasible. [2022]

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

Anti-PSMA CAR-engineered NK-92 Cells: An Off-the-shelf Cell Therapy for Prostate Cancer. [2021]

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

Systemic treatment with CAR-engineered T cells against PSCA delays subcutaneous tumor growth and prolongs survival of mice. [2021]

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

Dendritic cell-directed vaccination with a lentivector encoding PSCA for prostate cancer in mice. [2022]