FSHR-Targeted T Cell Therapy for Ovarian Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Waitlist Available
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
No Placebo Group
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.
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.
12345What 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.
12356Is 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.
12347Eligibility 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.
+12 more
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.
+15 more
Participant Groups
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.
10Treatment groups
Experimental Treatment
Group I: Intravenous treatment - Dose Level 5Experimental Treatment1 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 4Experimental Treatment1 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 3Experimental Treatment1 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 2Experimental Treatment1 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 1Experimental Treatment1 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 5Experimental Treatment1 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 4Experimental Treatment1 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 3Experimental Treatment1 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 2Experimental Treatment1 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 1Experimental Treatment1 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Moffitt Cancer CenterTampa, FL
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Who Is Running the Clinical Trial?
H. Lee Moffitt Cancer Center and Research InstituteLead Sponsor
Anixa Biosciences, Inc.Collaborator
References
Follicle-Stimulating Hormone Receptor Is Expressed by Most Ovarian Cancer Subtypes and Is a Safe and Effective Immunotherapeutic Target. [2021]To define the safety and effectiveness of T cells redirected against follicle-stimulating hormone receptor (FSHR)-expressing ovarian cancer cells.
Follicle-Stimulating Hormone Receptor as a Target in the Redirected T-cell Therapy for Cancer. [2018]Adoptive transfer of T cells engineered to express chimeric immunoreceptors is an effective strategy to treat hematologic cancers; however, the use of this type of therapy for solid cancers, such as ovarian cancer, remains challenging because a safe and effective immunotherapeutic target has not yet been identified. Here, we constructed and evaluated a novel redirected T-cell-based immunotherapy targeting human follicle-stimulating hormone receptor (FSHR), a highly conserved molecule in vertebrate animals with expression limited to gonadal tissues, ovarian cancer, and cancer-associated vasculature. Receptor ligand-based anti-FSHR immunoreceptors were constructed that contained small binding fragments from the ligand for FSHR, FSH, fused to T-cell transmembrane and T-cell signaling domains. Human T cells transduced to express anti-FSHR immunoreceptors were specifically immunoreactive against FSHR-expressing human and mouse ovarian cancer cell lines in an MHC-nonrestricted manner and mediated effective lysis of FHSR-expressing tumor cells, but not FSHR-deficient targets, in vitro. Similarly, the outgrowth of human ovarian cancer xenografts in immunodeficient mice was significantly inhibited by the adoptive transfer of FSHR-redirected T cells. Our experimental observations show that FSHR is a promising immunotherapeutic target for ovarian cancer and support further exploration of FSHR-targeted immune therapy approaches for patients with cancer.
A mAb against surface-expressed FSHR engineered to engage adaptive immunity for ovarian cancer immunotherapy. [2023]Despite advances in ovarian cancer (OC) therapy, recurrent OC remains a poor-prognosis disease. Because of the close interaction between OC cells and the tumor microenvironment (TME), it is important to develop strategies that target tumor cells and engage components of the TME. A major obstacle in the development of OC therapies is the identification of targets with expression limited to tumor surface to avoid off-target interactions. The follicle-stimulating hormone receptor (FSHR) has selective expression on ovarian granulosa cells and is expressed on 50%-70% of serous OCs. We generated mAbs targeting the external domain of FSHR using in vivo-expressed FSHR vector. By high-throughput flow analysis, we identified multiple clones and downselected D2AP11, a potent FSHR surface-targeted mAb. D2AP11 identifies important OC cell lines derived from tumors with different mutations, including BRCA1/2, and lines resistant to a wide range of therapies. We used D2AP11 to develop a bispecific T cell engager. In vitro addition of PBMCs and T cells to D2AP11-TCE induced specific and potent killing of different genetic and immune escape OC lines, with EC50s in the ng/ml range, and attenuated tumor burden in OC-challenged mouse models. These studies demonstrate the potential utility of biologics targeting FSHR for OC and perhaps other FSHR-positive cancers.
Application of chimeric antigen receptor-engineered T cells in ovarian cancer therapy. [2021]Due to the critical role of T cells in the immune surveillance of ovarian cancer, adoptive T-cell therapies are receiving increased attention as an immunotherapeutic approach for ovarian cancer. Chimeric antigen receptors (CARs), constructed by incorporating the single-chain Fv fragment to a T-cell signaling domain such as CD3 ζ or Fc receptor γ chain, endow T cell with nonmajor histocompatibility complex-restricted specificity. Dual specificity, trans-signaling CARs and affinity-tuned single-chain Fv fragment have broadened the applicability of CAR-engineered T-cell therapy and may be considered preferential to T cell receptor T-cell therapy in clinical care. As new insights into the CAR-engineered T cells have emerged over the last decade, we review the development of CAR T-cell therapy and discuss the progress and safety concerns regarding its translation from basic research into clinical care of ovarian cancer.
CAR-T cell therapy in ovarian cancer: from the bench to the bedside. [2019]Ovarian cancer (OC) is the most lethal gynecological malignancy and is responsible for most gynecological cancer deaths. Apart from conventional surgery, chemotherapy, and radiotherapy, chimeric antigen receptor-modified T (CAR-T) cells as a representative of adoptive cellular immunotherapy have received considerable attention in the research field of cancer treatment. CARs combine antigen specificity and T-cell-activating properties in a single fusion molecule. Several preclinical experiments and clinical trials have confirmed that adoptive cell immunotherapy using typical CAR-engineered T cells for OC is a promising treatment approach with striking clinical efficacy; moreover, the emerging CAR-Ts targeting various antigens also exert great potential. However, such therapies have side effects and toxicities, such as cytokine-associated and "on-target, off-tumor" toxicities. In this review, we systematically detail and highlight the present knowledge of CAR-Ts including the constructions, vectors, clinical applications, development challenges, and solutions of CAR-T-cell therapy for OC. We hope to provide new insight into OC treatment for the future.
CAR-T Cells Targeting TSHR Demonstrate Safety and Potent Preclinical Activity Against Differentiated Thyroid Cancer. [2022]Chimeric antigen receptor T cells (CAR-Ts) have demonstrated remarkable efficacy in hematological cancers but have not yet translated in treating solid tumors. The significant hurdles limiting CAR-T therapy were from a paucity of differentially expressed cell surface molecules on solid tumors that can be safely targeted. Here, we present TSH receptor (TSHR) as a putative target for CAR-T therapy of differentiated thyroid cancer (DTC).
Follicle-stimulating hormone polypeptide modified nanoparticle drug delivery system in the treatment of lymphatic metastasis during ovarian carcinoma therapy. [2014]Traditional chemotherapy drugs have an obvious drawback of nonspecific biodistribution in treating ovarian cancer. Follicle-stimulating hormone receptor (FSHR), a G-protein coupled receptor which is mainly expressed in reproductive system, is an important drug target in developing novel therapeutics.