FSHR-Targeted T Cell Therapy for Ovarian Cancer

Overseen By Ashley K O'Neil

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must be taking: Platinum-based chemotherapy

Disqualifiers: Hepatitis, HIV, Bowel obstruction, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

10 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment that uses a patient's own modified immune cells to target and kill cancer cells. It focuses on patients whose ovarian, fallopian tube, or primary peritoneal cancer has come back or hasn't responded to other treatments.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you must stop all current medications. However, hormonal therapy must be stopped at least 1 week before T-cell infusion, and no anticancer therapy is allowed in the 3 weeks before the T-cell infusion. Continuation of hormone replacement therapy is permitted.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop all current medications, but hormonal therapy must be stopped at least 1 week before the T-cell infusion. You should also not have any anticancer therapy in the 3 weeks before the T-cell infusion.

What data supports the idea that FSHR-Targeted T Cell Therapy for Ovarian Cancer is an effective treatment?

The available research shows that FSHR-Targeted T Cell Therapy is effective in treating ovarian cancer. Studies have demonstrated that T cells engineered to target the follicle-stimulating hormone receptor (FSHR) can specifically attack ovarian cancer cells that express this receptor. In experiments, these T cells were able to significantly reduce the growth of ovarian cancer in mice. Additionally, the therapy was shown to effectively kill cancer cells in laboratory settings without harming non-cancerous cells. This suggests that FSHR-Targeted T Cell Therapy could be a promising treatment for ovarian cancer, offering a targeted approach that minimizes damage to healthy tissues. ^{1 2 3 4 5}

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

Research shows that T cells engineered to target the follicle-stimulating hormone receptor (FSHR) can effectively attack ovarian cancer cells in lab settings and reduce tumor growth in mice. This suggests that FSHR-targeted T cell therapy could be a promising approach for treating ovarian cancer. ^{1 2 3 4 5}

What safety data exists for FSHR-targeted T cell therapy for ovarian cancer?

The safety data for FSHR-targeted T cell therapy, also known as Follicle Stimulating Hormone Receptor T Cells or FSHCER T cells, is primarily preclinical. Studies have shown that these engineered T cells specifically target FSHR-expressing ovarian cancer cells without affecting FSHR-deficient cells, indicating a potential for safe application. In mouse models, FSHR-redirected T cells significantly inhibited tumor growth, suggesting a promising safety profile. However, the data is mostly from preclinical studies, and further clinical trials are needed to fully establish safety in humans. ^{1 2 3 5 6}

Is FSHR-targeted T cell therapy safe for humans?

Research suggests that FSHR-targeted T cell therapy is a promising approach for treating ovarian cancer, with studies showing it can specifically target cancer cells without affecting healthy cells. However, like other similar therapies, it may have side effects, and more research is needed to fully understand its safety in humans. ^{1 2 3 5 6}

Is FSHR-Targeted T Cell Therapy a promising treatment for ovarian cancer?

Yes, FSHR-Targeted T Cell Therapy is promising for ovarian cancer because it targets a specific receptor found on most ovarian cancer cells, making it effective in killing cancer cells while sparing healthy ones. This approach has shown success in lab studies and animal models, suggesting it could be a valuable treatment option. ^{1 2 3 4 7}

What makes FSHR-targeted T cell therapy unique for ovarian cancer treatment?

FSHR-targeted T cell therapy is unique because it uses specially engineered T cells to target the follicle-stimulating hormone receptor (FSHR), which is found on ovarian cancer cells but not on most normal cells, making it a promising and specific immunotherapy for ovarian cancer. ^{1 2 3 4 7}

Research Team

Robert M Wenham, MD, MS, FACOG, FACS

Principal Investigator

Moffitt Cancer Center

Eligibility Criteria

This trial is for adults with recurrent ovarian, fallopian tube, or primary peritoneal cancer who've had at least one platinum-based and two other chemotherapy treatments. They must have a life expectancy of over 3 months, no recent anticancer therapy or immunotherapy, and agree to use contraception. The cancer must express FSHR antigen.

Inclusion Criteria

My cancer did not respond well to platinum-based treatments.

I have had 1 platinum-based and at least 2 other chemotherapy treatments for ovarian, peritoneal, or fallopian tube cancer.

Life expectancy of at least 3 months.

Exclusion Criteria

I have had issues like an abdominal fistula, gut perforation, or abscess.

Current lactation or pregnancy.

I do not have any serious infections, except for a simple UTI.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive one infusion of FSHCER T cells at various dose levels, administered either intravenously or intraperitoneally

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 15 years

Treatment Details

Interventions

• Follicle Stimulating Hormone Receptor T Cells

Trial Overview The study tests the safety of genetically modified T cells targeting the FSH receptor in patients with certain types of ovarian cancers. It explores treatment effectiveness both with and without additional chemotherapy.

Participant Groups

Group I: Intravenous treatment - Dose Level 5 Experimental Treatment 1 Intervention

Participants will receive one infusion of Follicle-Stimulating Hormone Receptor T (FSHCER T) cells at a dose of 1 x 10\^7 by Intravenous (IV).

Group II: Intravenous treatment - Dose Level 4 Experimental Treatment 1 Intervention

Participants will receive one infusion of Follicle-Stimulating Hormone Receptor T (FSHCER T) cells at a dose of 3 x 10\^6 by Intravenous (IV).

Group III: Intravenous treatment - Dose Level 3 Experimental Treatment 1 Intervention

Participants will receive one infusion of Follicle-Stimulating Hormone Receptor T (FSHCER T) cells at a dose of 1 x 10\^6 by Intravenous (IV).

Group IV: Intravenous treatment - Dose Level 2 Experimental Treatment 1 Intervention

Participants will receive one infusion of Follicle-Stimulating Hormone Receptor T (FSHCER T) cells at a dose of 3 x 10\^5 by Intravenous (IV).

Group V: Intravenous treatment - Dose Level 1 Experimental Treatment 1 Intervention

Participants will receive one infusion of Follicle-Stimulating Hormone Receptor T (FSHCER T) cells at a dose of 1 x 10\^5 by Intravenous (IV).

Group VI: Intraperitoneal treatment- Dose Level 5 Experimental Treatment 1 Intervention

Participants will receive one infusion of Follicle-Stimulating Hormone Receptor T (FSHCER T) cells at a dose of 1 x 10\^7. Intraperitoneal: Infusion will be administered through a thin membrane of the abdominal cavity.

Group VII: Intraperitoneal treatment- Dose Level 4 Experimental Treatment 1 Intervention

Participants will receive one infusion of Follicle-Stimulating Hormone Receptor T (FSHCER T) cells at a dose of 3 x 10\^6. Intraperitoneal: Infusion will be administered through a thin membrane of the abdominal cavity.

Group VIII: Intraperitoneal treatment- Dose Level 3 Experimental Treatment 1 Intervention

Participants will receive one infusion of Follicle-Stimulating Hormone Receptor T (FSHCER T) cells at a dose of 1 x 10\^6. Intraperitoneal: Infusion will be administered through a thin membrane of the abdominal cavity.

Group IX: Intraperitoneal treatment- Dose Level 2 Experimental Treatment 1 Intervention

Participants will receive one infusion of Follicle-Stimulating Hormone Receptor T (FSHCER T) cells at a dose of 3 x 10\^5. Intraperitoneal: Infusion will be administered through a thin membrane of the abdominal cavity.

Group X: Intraperitoneal treatment- Dose Level 1 Experimental Treatment 1 Intervention

Participants will receive one infusion of Follicle-Stimulating Hormone Receptor T (FSHCER T) cells at a dose of 1 x 10\^5. Intraperitoneal: Infusion will be administered through a thin membrane of the abdominal cavity.

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Anixa Biosciences, Inc.

Collaborator

Trials

2

Recruited

60+

Findings from Research

T cells engineered to target the follicle-stimulating hormone receptor (FSHR) showed significant therapeutic effects against various ovarian cancer types, leading to tumor rejection and increased survival in mouse models without causing toxicity.

FSHR is specifically expressed in ovarian cancer tissues but not in healthy non-ovarian tissues, making it a promising target for T cell therapies, which also demonstrated the ability to persist as memory cells without exhaustion during advanced disease stages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Follicle-Stimulating Hormone Receptor Is Expressed by Most Ovarian Cancer Subtypes and Is a Safe and Effective Immunotherapeutic Target. Perales-Puchalt, A., Svoronos, N., Rutkowski, MR., et al.[2021]

A novel T-cell immunotherapy targeting the follicle-stimulating hormone receptor (FSHR) has shown promise in treating ovarian cancer, as it specifically attacks FSHR-expressing cancer cells while sparing healthy cells.

In laboratory studies, T cells engineered to express anti-FSHR receptors effectively killed ovarian cancer cells and significantly inhibited tumor growth in mouse models, suggesting that FSHR could be a safe and effective target for immunotherapy in solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Follicle-Stimulating Hormone Receptor as a Target in the Redirected T-cell Therapy for Cancer. Urbanska, K., Stashwick, C., Poussin, M., et al.[2018]

The study developed a monoclonal antibody (mAb) targeting the follicle-stimulating hormone receptor (FSHR), which is selectively expressed in 50%-70% of serous ovarian cancers, allowing for targeted therapy with reduced off-target effects.

The bispecific T cell engager (D2AP11-TCE) demonstrated potent and specific killing of various ovarian cancer cell lines in vitro and reduced tumor burden in mouse models, indicating its potential as an effective treatment strategy for ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A mAb against surface-expressed FSHR engineered to engage adaptive immunity for ovarian cancer immunotherapy. Bordoloi, D., Bhojnagarwala, PS., Perales-Puchalt, A., et al.[2023]

Adoptive T-cell therapies, particularly CAR T-cell therapy, are gaining attention for their potential to enhance immune responses against ovarian cancer, leveraging T cells' critical role in immune surveillance.

Recent advancements, such as dual specificity CARs and affinity-tuned single-chain Fv fragments, may improve the effectiveness and safety of CAR T-cell therapies compared to traditional T cell receptor therapies in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of chimeric antigen receptor-engineered T cells in ovarian cancer therapy. Zhang, M., Zhang, DB., Shi, H.[2021]

Chimeric antigen receptor-modified T (CAR-T) cell therapy shows promising clinical efficacy in treating ovarian cancer, as supported by various preclinical experiments and clinical trials.

While CAR-T therapy offers a novel approach to cancer treatment, it is associated with side effects and toxicities, including cytokine release syndrome and 'on-target, off-tumor' effects, which need to be managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T cell therapy in ovarian cancer: from the bench to the bedside. Zhu, X., Cai, H., Zhao, L., et al.[2019]

The TSH receptor (TSHR) is highly expressed in a majority of thyroid cancer cases, making it a promising target for CAR-T therapy, particularly in differentiated thyroid cancer (DTC).

Three novel anti-TSHR CAR-Ts were developed, with the K1-70 CAR-T showing significant antitumor activity in vitro and therapeutic efficacy in a mouse model without apparent toxicity, suggesting its potential for safe application in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cells Targeting TSHR Demonstrate Safety and Potent Preclinical Activity Against Differentiated Thyroid Cancer. Li, H., Zhou, X., Wang, G., et al.[2022]

The study developed a targeted nanoparticle (FSHP-NP) that specifically binds to the follicle-stimulating hormone receptor (FSHR), which is highly expressed in ovarian cancer, improving the delivery of the chemotherapy drug paclitaxel (PTX).

FSHP-NP-PTX demonstrated significantly enhanced anti-tumor effects in both cell cultures and animal models, leading to reduced lymph node size and weight, indicating its potential as a more effective treatment for ovarian cancer compared to traditional chemotherapy methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Follicle-stimulating hormone polypeptide modified nanoparticle drug delivery system in the treatment of lymphatic metastasis during ovarian carcinoma therapy. Fan, L., Chen, J., Zhang, X., et al.[2014]

References

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

Follicle-Stimulating Hormone Receptor Is Expressed by Most Ovarian Cancer Subtypes and Is a Safe and Effective Immunotherapeutic Target. [2021]

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

Follicle-Stimulating Hormone Receptor as a Target in the Redirected T-cell Therapy for Cancer. [2018]

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

A mAb against surface-expressed FSHR engineered to engage adaptive immunity for ovarian cancer immunotherapy. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Application of chimeric antigen receptor-engineered T cells in ovarian cancer therapy. [2021]

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

CAR-T cell therapy in ovarian cancer: from the bench to the bedside. [2019]

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

CAR-T Cells Targeting TSHR Demonstrate Safety and Potent Preclinical Activity Against Differentiated Thyroid Cancer. [2022]

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

Follicle-stimulating hormone polypeptide modified nanoparticle drug delivery system in the treatment of lymphatic metastasis during ovarian carcinoma therapy. [2014]