CAR T-Cell Therapy for Prostate Cancer

Overseen By Naomi Haas, MD

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: University of Pennsylvania

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day (Day 0)

23 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a single center, single arm Phase I study to establish the safety and feasibility of intravenously administered lentivirally transduced dual PSMA-specific/ TGFβ-resistant CAR modified autologous T cells (CART-PSMA-TGFβRDN cells) in patients with metastatic castrate resistant prostate cancer.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have had treatment with certain immune therapies within 2 months before joining. You also cannot be on high-dose steroids, but low doses are allowed.

What data supports the effectiveness of the treatment CART-PSMA-TGFβRDN cells for prostate cancer?

Research shows that CAR T-cell therapy targeting PSMA (a protein found in prostate cancer cells) can effectively eliminate prostate cancer in animal models. Additionally, modifying these CAR T-cells to block TGF-β (a protein that helps cancer evade the immune system) enhances their ability to fight prostate cancer, leading to increased cell proliferation and tumor eradication in aggressive cancer models. ^{1 2 3 4 5}

Is CAR T-Cell Therapy for Prostate Cancer safe for humans?

CAR T-Cell Therapy targeting PSMA with a dominant-negative TGFβ receptor has shown to be safe and feasible in early studies for prostate cancer. However, challenges like dose-limiting toxicity and immune-related side effects have been noted in early trials, indicating the need for careful monitoring. ^{2 3 6 7 8}

What makes the CART-PSMA-TGFβRDN cell treatment unique for prostate cancer?

The CART-PSMA-TGFβRDN cell treatment is unique because it uses genetically engineered T-cells that target the prostate-specific membrane antigen (PSMA) on cancer cells and includes a dominant-negative TGFβ receptor to enhance safety and effectiveness by overcoming the tumor's immunosuppressive environment. ^{2 3 4 6 8}

Research Team

Naomi Haas, MD

Principal Investigator

Universtiy of Pennsylvania

Eligibility Criteria

Men over 18 with advanced prostate cancer that's resistant to hormone therapy and has spread, showing at least 10% of tumor cells expressing PSMA. They should be relatively healthy (ECOG status 0-1), have good organ function, no severe heart issues or active infections like hepatitis B/C or HIV, not on high-dose steroids, and haven't had more than four prior treatments for this cancer stage.

Inclusion Criteria

My tumor shows high PSMA levels on a biopsy.

My cancer has spread to my bones or other parts of my body and can be seen on scans.

I have had treatment for advanced prostate cancer that no longer responds to hormonal therapy.

Exclusion Criteria

I have severe heart problems as defined by the NYHA.

I do not have a condition that increases risk of severe immune or nerve side effects.

I haven't had immune therapy for cancer in the last 2 months, except for cancer vaccines.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of lentivirally transduced CART-PSMA-TGFβRDN cells, with or without lymphodepleting chemotherapy, depending on cohort assignment

1 day (Day 0)

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and clinical anti-tumor effects

6 months

Long-term follow-up

Participants are monitored for long-term safety and adverse events

15 years

Treatment Details

Interventions

• CART-PSMA-TGFβRDN cells

Trial Overview The trial is testing a new type of cell therapy where the patient's own immune cells are modified to target prostate cancer cells better. These special CART-PSMA-TGFβRDN cells are given through an IV after preparing the body with drugs Fludarabine and Cyclophosphamide.

Participant Groups

Group I: Cohort 4 Experimental Treatment 3 Interventions

CART-PSMA-TGFβRDN cells 0.70-1.00 x 10\^8 Day 0

Group II: Cohort 3 Experimental Treatment 3 Interventions

CART-PSMA-TGFβRDN cells at the MTD (established by Cohorts 1-2) on day 0

Group III: Cohort 2 Experimental Treatment 1 Intervention

CART-PSMA-TGFβRDN cells 1-3x10\^8 Day 0

Group IV: Cohort 1 Experimental Treatment 1 Intervention

CART-PSMA-TGFβRDN cells 1-3x10\^7 Day 0

Group V: Cohort -3 Experimental Treatment 3 Interventions

CART-PSMA-TGFβRDN cells 1-3x10\^7 Day 0

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Findings from Research

A novel CAR T cell therapy targeting a new epitope in the prostate-specific membrane antigen (PSMA) showed promising results in eradicating established prostate cancer in a preclinical mouse model.

Combining the PSMA CAR T cells with low-dose docetaxel chemotherapy significantly enhanced tumor growth inhibition, suggesting that this combination could be an effective treatment strategy for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PSMA-Directed CAR T Cells Combined with Low-Dose Docetaxel Treatment Induce Tumor Regression in a Prostate Cancer Xenograft Model. Alzubi, J., Dettmer-Monaco, V., Kuehle, J., 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]

Chimeric antigen receptor (CAR) T cells targeting prostate-specific membrane antigen (PSMA) effectively eliminate prostate cancer in various animal models, demonstrating strong antitumor activity and specificity.

The success of these PSMA-targeted T cells in eradicating tumors is linked to their survival in the body for at least one week, suggesting that long-term persistence is crucial for achieving durable remissions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted elimination of prostate cancer by genetically directed human T lymphocytes. Gade, TP., Hassen, W., Santos, E., et al.[2018]

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]

References

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

PSMA-Directed CAR T Cells Combined with Low-Dose Docetaxel Treatment Induce Tumor Regression in a Prostate Cancer Xenograft Model. [2020]

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

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

3. England pubmed.ncbi.nlm.nih.gov

Bispecific PSMA antibodies and CAR-T in metastatic castration-resistant prostate cancer. [2023]

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

Targeted elimination of prostate cancer by genetically directed human T lymphocytes. [2018]

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

Dominant-Negative TGF-β Receptor Enhances PSMA-Targeted Human CAR T Cell Proliferation And Augments Prostate Cancer Eradication. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Advanced generation anti-prostate specific membrane antigen designer T cells for prostate cancer immunotherapy. [2018]

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

Retargeting of T lymphocytes to PSCA- or PSMA positive prostate cancer cells using the novel modular chimeric antigen receptor platform technology "UniCAR". [2021]