CAR T Cell Therapy for Prostate Cancer

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must be taking: LHRH agonist/antagonist

Disqualifiers: Arrhythmia, Optic neuritis, Stroke, others

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

Compensation: Varies

Number of Visits: 2

Duration: 1 day

14 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that prior chemotherapy is allowed if at least 2 weeks have passed before a procedure called leukapheresis. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment PSCA-CAR T Cells for prostate cancer?

Research shows that CAR T cell therapy, which involves modifying a patient's own immune cells to better attack cancer, has been successful in treating blood cancers and is now being tested for prostate cancer. The prostate stem cell antigen (PSCA) is a promising target for this therapy because it is found on prostate cancer cells, and early studies in mice have shown that PSCA-CAR T cells can slow tumor growth and extend survival. ^{1 2 3 4 5}

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

Research on CAR T cell therapy, including PSCA-CAR T cells, shows promising safety results in preclinical studies, with no observed toxicities in normal tissues in mouse models. Additionally, PSMA-targeting CAR T cells have been found to be safe and feasible in prostate cancer, although challenges like dose-limiting toxicity and immune-related side effects have been noted in early clinical studies. ^{1 3 5 6 7}

How is CAR T Cell Therapy for Prostate Cancer different from other treatments?

CAR T Cell Therapy for Prostate Cancer is unique because it uses genetically engineered T cells to specifically target and attack prostate cancer cells by recognizing a protein called PSCA on their surface. This approach is different from traditional treatments as it aims to harness the body's immune system to fight cancer, potentially offering a new option for patients with advanced prostate cancer. ^{1 2 3 8 9}

What is the purpose of this trial?

This trial studies the safety and best dose of specially modified immune cells in treating patients with advanced prostate cancer that doesn't respond to standard treatments. The modified immune cells are designed to find and kill cancer cells. The study aims to determine how well this treatment works and its side effects.

Research Team

Tanya B Dorff

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

Men with advanced prostate cancer that's resistant to hormone therapy and has spread, who are fit enough for treatment (ECOG 0-2), have PSCA+ tumors, and can consent. They must not have certain central nervous system conditions, uncontrolled infections, HIV/hepatitis B/C, bleeding disorders or recent strokes. Participants need proper liver/kidney function and agree to birth control during the study.

Inclusion Criteria

All participants must have the ability to understand and the willingness to sign a written informed consent

Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2

Documented PSCA+ tumor expression as evaluated by City of Hope (COH) Pathology Care

Exclusion Criteria

You have a history of optic neuritis or other immune or inflammatory diseases that affect the brain and spinal cord, including seizures.

You have a known bleeding disorder like von Willebrand's disease or hemophilia.

You have had a stroke or bleeding in the brain within the past 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Patients may receive a lymphodepleting regimen including fludarabine and cyclophosphamide intravenously

3-5 days

Daily visits for lymphodepletion

Treatment

Patients receive autologous anti-PSCA-CAR T lymphocytes intravenously

1 day

1 visit (in-person) for infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 15 years

Day 1, every 2 days for up to 14 days, weekly for up to 1 month, every month for up to 1 year, and then annually

Treatment Details

Interventions

• PSCA-CAR T Cells

Trial Overview The trial is testing a new type of immune cell therapy called PSCA-CAR T cells on men with metastatic castration-resistant prostate cancer. These cells are genetically modified to attack prostate cancer cells by recognizing a specific antigen present on their surface.

Participant Groups

Group I: Treatment (PSCA CAR T cells) Experimental Treatment 4 Interventions

Patients may receive lymphodepleting regimen (either standard or modified) including fludarabine IV on days -5 to -3 and cyclophosphamide IV on days -5 to -3 or on days -4 and/or -3. The study PI and the protocol team will choose a chemotherapy regimen, for lymphodepletion prior to the PSCA-CAR T cell infusion (with the exception of cohorts 1 and -1 which will not receive lymphodepletion), based on the research participant's disease type and prior therapies. Patients then receive autologous anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T lymphocytes IV over 10-15 minutes at day 0.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

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]

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]

References

1. 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]

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. England pubmed.ncbi.nlm.nih.gov

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

4. Switzerland pubmed.ncbi.nlm.nih.gov

Challenges and Prospects of Chimeric Antigen Receptor T-cell Therapy for Metastatic Prostate Cancer. [2021]

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

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

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

Pre-conditioning modifies the TME to enhance solid tumor CAR T cell efficacy and endogenous protective immunity. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

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

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]

9. England pubmed.ncbi.nlm.nih.gov

CAR-T cell therapy: a potential new strategy against prostate cancer. [2023]