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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for men with advanced prostate cancer that has spread to the bones and no longer responds to standard treatments. The focus is on using modified immune cells, called T cells, specifically MSGV1-PSCA-8T28Z, to target cancer cells more effectively. Researchers aim to determine if this treatment is safe and can help control the cancer. It suits those with prostate cancer resistant to hormone therapy, who have received previous chemotherapy, and are currently taking medication for bone metastases. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that treatments using MSGV1-PSCA-8T28Z, specially designed immune cells, are under study for their safety in humans. In one study, these modified cells, known as CAR-T cells, showed potential in treating prostate cancer that has spread to the bones. The main focus is to ensure these cells are safe and effective.

Early results suggest that this treatment is generally well-tolerated. However, since it remains in the early testing stages, all possible side effects are not yet known. The trial aims to find the safest dose by starting with low doses and gradually increasing them, allowing for close monitoring of any negative reactions.

As a phase 1 trial, the primary goal is to assess safety. These trials usually involve a small number of participants and are a crucial first step in understanding how the treatment works in humans. Participants receive close monitoring for any side effects, enabling researchers to make necessary adjustments and ensure the treatment is as safe as possible. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for prostate cancer, which often include surgery, radiation, and hormone therapy, MSGV1-PSCA-8T28Z is a cutting-edge approach using modified immune cells. Researchers are excited because this treatment involves engineering a patient's own immune cells to better recognize and attack prostate cancer cells, potentially offering a more targeted and personalized therapy. The unique mechanism of action, which differs from broad systemic treatments, holds promise for fewer side effects and improved effectiveness. This innovative approach could mark a significant advancement in prostate cancer care by harnessing the body's own defenses in a novel way.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

Research has shown that MSGV1-PSCA-8T28Z, a treatment using specially modified immune cells, could be promising for bone metastatic prostate cancer. Participants in this trial will receive MSGV1-PSCA-8T28Z after lymphodepletion with cyclophosphamide and fludarabine. Studies have demonstrated that these engineered cells specifically target a protein called PSCA in prostate cancer cells and effectively slow tumor growth in bones. Early trials with similar treatments showed significant tumor control. This method harnesses the body's immune system to fight cancer, representing a cutting-edge approach in cancer treatment. While more remains to be learned, these early results offer hope for those with limited treatment options. ^{1 2 3 5 6}

Who Is on the Research Team?

Jingsong Zhang, MD

Principal Investigator

Moffitt Cancer Center

Daniel Abate-Daga, PhD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06193486

Study Details | NCT06193486 | Autologous Gamma Delta T ... This is a phase 1 single center clinical trial for patients with end stage Metastatic Castration Resistant Prostate Cancer who have progressed through standard ...

2. jitc.bmj.com jitc.bmj.com/content/12/Suppl_2/A733

639 Phase I clinical trial of autologous gamma/delta ... This is a single institution phase 1 study in M1b CRPC to assess the safety of autologous gamma/delta-enriched T cells genetically modified to express a CAR ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10156127/

γδ-Enriched CAR-T cell therapy for bone metastatic ... Together, the data reveal that γδ T cell–based CAR therapies effectively mitigate bone metastatic prostate tumors and that the infusion of anti- ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12421624/

Comparative efficacy and safety of PSCA CAR-engineered ... This study directly compares the efficacy of prostate stem cell antigen (PSCA) chimeric antigen receptor (CAR)-Vδ1 γδ T cells with PSCA CAR-Vδ2 ...

5. researchgate.net researchgate.net/publication/385556705_639_Phase_I_clinical_trial_of_autologous_gammadelta-enriched_chimeric_antigen_receptor_CAR-T_cells_to_target_prostate_stem_cell_antigen_PSCA_in_patients_with_bone_metastatic_prostate_cancer

(PDF) 639 Phase I clinical trial of autologous gamma/delta ... We have previously demonstrated that γδ Chimeric Antigen Receptor (CAR) T cells targeting prostate stem cell antigen (PSCA) led to significant ...

6. moffitt.org moffitt.org/for-healthcare-professionals/clinical-perspectives/clinical-perspectives-story-archive/moffitt-researchers-investigating-car-t-therapy-feasibility-in-metastatic-castration-resistant-prostate-cancer/

Moffitt Researchers Investigating CAR T Therapy ... Moffitt researchers aim to improve the efficacy and safety of CAR-T therapy with infusion of freshly produced gamma delta enriched CAR-T cells.