Engineered T Cell Therapy for Prostate Cancer

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Radiopharmaceuticals, Corticosteroids, Immunosuppressives, others

Disqualifiers: Non-prostate cancer, Autoimmune diseases, Cardiac disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

13 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase I study which will test the safety of different doses of the patients own immune cells which have been changed to help recognize and destroy the cancer cells. The investigators want to find out what effects, good and/or bad, it has on the body and on the prostate cancer. The immune cells (T cells) used in this study will be the patients own immune cells. They will be removed from the patients blood, changed in the laboratory, and then put back into their body. T cells help the body fight infections. These cells may also kill cancer cells in some cases. Right now the patients T cells are unable to kill the cancer cells. For this reason, the physician will change the T cells by putting in a gene so that they may be able to better recognize and kill the prostate cancer cells. A gene is a portion of information which comes from the DNA and tells the cell what to do. This gene will be put into the patients T cells by a weakened virus. It is hoped that this approach will help the T cells recognize the prostate cancer tumor cells and possibly kill them. The investigators have found that T cells modified in this way were able to cure a cancer similar to Chronic Lymphocytic Leukemia in mice. However, this is an entirely new treatment for prostate cancer and it is not known if it will have any beneficial or unexpected harmful effects.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does mention that certain treatments and medications, like some radiopharmaceuticals and alternative medicine treatments for prostate cancer, should not be taken within four weeks before starting the study. It's best to discuss your specific medications with the study team.

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

Research shows that engineered T cells, which are modified to target specific cancer markers, have been successful in treating other cancers like melanoma by enhancing the body's immune response to tumors. Additionally, a similar approach using CAR-T cells targeting a specific prostate cancer antigen demonstrated strong anti-tumor activity in preclinical models, suggesting potential effectiveness for prostate cancer. ^{1 2 3 4 5}

Is engineered T cell therapy generally safe for humans?

Engineered T cell therapies, like CAR-T cells, have shown success in treating cancer but can cause significant side effects, such as on-target toxicity (damage to healthy tissues) and cytokine release syndrome (a severe immune reaction). Safety measures, like failsafe switches, are being developed to reduce these risks. ^{3 6 7 8 9}

How is the engineered T cell therapy for prostate cancer different from other treatments?

This treatment uses specially engineered T cells to target prostate cancer cells by recognizing specific proteins on their surface, offering a more targeted approach compared to traditional therapies. It represents a novel form of immunotherapy that modifies the patient's own immune cells to better attack cancer cells. ^{1 2 3 10 11}

Research Team

Susan F. Slovin, MD, Ph.D

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for men over 18 with advanced prostate cancer that has spread and is resistant to hormone therapy. They must have a good performance status, adequate organ function, no HIV or hepatitis, and agree to use contraception. Excluded are those with other cancers within five years (except non-melanoma skin cancer), severe heart or lung disease, recent radiation therapy, immunosuppressive treatments, certain medications for prostate cancer, active CNS metastases, infections requiring antibiotics shortly before the trial starts.

Inclusion Criteria

I am a man and older than 18.

I am mostly able to care for myself but may not be able to do active work.

My cancer has spread to my bones, confirmed by scans.

Exclusion Criteria

I have not had any cancer other than non-melanoma skin cancer in the last 5 years.

I have had radiation, more than one chemotherapy, or certain medications recently.

My cancer has spread to my brain or spinal cord and is causing symptoms.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pretreatment

Participants receive pretreatment with cyclophosphamide before T cell infusion

1 day

Treatment

Participants receive engineered autologous T cells targeted to PSMA

1 day

Follow-up

Participants are monitored for safety and effectiveness after T cell infusion

4 weeks

Treatment Details

Interventions

• cyclophosphamide
• engineered autologous T cells

Trial Overview The study tests different doses of modified T cells from the patient's own body designed to target and kill prostate cancer cells. It's a phase I safety trial aiming to see how these engineered immune cells affect both the body and the progression of prostate cancer.

Participant Groups

Group I: autologous T cells & cyclophosphamide. Experimental Treatment 2 Interventions

This is a phase I dose escalation study to assess the safety and tolerability using increasing doses of engineered autologous T cells targeted to Prostate-Specific Membrane Antigen (PSMA) administered one day after pretreatment with cyclophosphamide.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Findings from Research

Recent advancements in delivering transgenes to human T cells have improved the effectiveness of T cell therapies for cancer, allowing for the creation of T cells that can specifically target tumors.

While genetically modified T cells have shown success in clinical trials, they can also cause significant on-target toxicity, highlighting the need for careful selection of target antigens and strategies to manage potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineered T cells for anti-cancer therapy. Turtle, CJ., Hudecek, M., Jensen, MC., et al.[2021]

The study identified STEAP2 as a promising target for CAR-T therapy in prostate cancer due to its high expression on tumor cells and limited presence in normal tissues, reducing the risk of off-target effects.

The engineered CAR-T therapy, AZD0754, showed strong anti-tumor activity in both laboratory and mouse models, demonstrating its potential as a safe and effective treatment option for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of AZD0754, a dnTGFβRII-armored, STEAP2-targeted CAR-T cell therapy, in prostate cancer. Zanvit, P., van Dyk, D., Fazenbaker, C., et al.[2023]

CAR-T cell therapies have shown significant clinical success in treating cancer by effectively targeting tumor-associated antigens, leading to complete and durable responses in many patients during early trials.

Despite their effectiveness, there are safety concerns regarding potential toxicities from engineered cells, prompting the exploration of strategies like integrating failsafe switches to enhance safety in cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineering Hematopoietic Cells for Cancer Immunotherapy: Strategies to Address Safety and Toxicity Concerns. Resetca, D., Neschadim, A., Medin, JA.[2018]

Engineered T cell therapies, like CAR T cells and TCR T cell therapies, have shown remarkable efficacy in treating certain blood cancers, highlighting their potential as a powerful tool in cancer immunotherapy.

However, these therapies also pose unique safety challenges, such as cytokine release syndrome and neurotoxicity, which require careful nonclinical safety assessments to ensure patient safety during development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonclinical safety assessment of engineered T cell therapies. Lebrec, H., Maier, CC., Maki, K., et al.[2022]

T-cell receptor gene therapy shows promise in redirecting T lymphocytes to target tumors, leading to encouraging clinical responses in previously incurable cancers, but it faces significant challenges in ensuring safety and efficacy.

Identifying specific tumor epitopes that can effectively target cancer cells while avoiding damage to normal tissues is crucial, and there is a need for improved preclinical methods to assess potential risks associated with this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cell receptor gene therapy--ready to go viral? Karpanen, T., Olweus, J.[2021]

References

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

Anti-prostate specific membrane antigen designer T cells for prostate cancer therapy. [2018]

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

The adoptive transfer of cultured T cells for patients with metastatic melanoma. [2013]

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

Engineered T cells for anti-cancer therapy. [2021]

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

Immunotherapy of cancer using systemically delivered gene-modified human T lymphocytes. [2014]

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

Antitumor activity of AZD0754, a dnTGFβRII-armored, STEAP2-targeted CAR-T cell therapy, in prostate cancer. [2023]

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

Engineering Hematopoietic Cells for Cancer Immunotherapy: Strategies to Address Safety and Toxicity Concerns. [2018]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Nonclinical safety assessment of engineered T cell therapies. [2022]

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

Bioactivity and Safety of IL13Rα2-Redirected Chimeric Antigen Receptor CD8+ T Cells in Patients with Recurrent Glioblastoma. [2023]

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

T-cell receptor gene therapy--ready to go viral? [2021]

10. England pubmed.ncbi.nlm.nih.gov

Biofabrication of 3D breast cancer models for dissecting the cytotoxic response of human T cells expressing engineered MAIT cell receptors. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Engineered T cells: the promise and challenges of cancer immunotherapy. [2023]