E7 TCR-T Cells for HPV-Related Cancer

Recruiting at 2 trial locations

Overseen By Tobi Adewale

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Rutgers, The State University of New Jersey

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Prior systemic therapy, Uncontrolled illness, Immunodeficiency, Severe autoimmune, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: 2

Duration: 1 day

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment using genetically engineered T cells to target and fight HPV-related cancers. The goal is to determine if these E7 TCR-T cells can shrink or eliminate tumors before patients undergo standard treatments like surgery or chemoradiation. It is specifically for individuals with HPV-related cancers who have not received prior systemic treatment for this condition. Participants will have their own T cells collected, modified, and then infused back to enhance their body's ability to combat the cancer. The trial aims to assess the treatment's effectiveness and its impact on long-term survival without delaying standard cancer treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, participants on immunosuppressive drugs, including corticosteroids, are not eligible unless they meet specific criteria. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that E7 TCR-T cells could help treat cancers related to HPV. These cells are specially designed to find and attack cancer cells with the HPV E7 marker. In earlier studies, E7 TCR-T cells proved safe and effective, particularly for hard-to-treat HPV-16 positive cancers. Patients who received this treatment saw their tumors shrink.

Importantly, the treatment was well-tolerated, meaning patients did not experience severe side effects that would make it unsafe. While some side effects can occur, the safety data so far supports further research into E7 TCR-T cells as a promising treatment for HPV-related cancers. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for HPV-related cancer?

Unlike the standard treatments for HPV-related cancers, which often include surgery, radiation, and chemotherapy, E7 TCR-T cells offer a novel approach by harnessing the body's immune system. This treatment uses genetically modified T cells that are designed to specifically target and destroy cancer cells expressing the E7 protein, a common feature in HPV-related cancers. Researchers are excited about this treatment because it represents a targeted and potentially more effective way to fight cancer with fewer side effects compared to traditional methods. Additionally, the use of aldesleukin alongside these T cells may enhance their ability to persist and function within the body, increasing the treatment's overall efficacy.

What evidence suggests that E7 TCR-T cells could be an effective treatment for HPV-related cancer?

Research has shown that a new treatment using E7 TCR-T cells may help fight cancers linked to HPV. In a study, these specially engineered cells shrank tumors in cancers caused by HPV-16. They target a specific protein, E7, found in these tumors, aiming to reduce or eliminate them. Early results suggest this method can be effective, with some patients experiencing tumor reduction. Although still in the early stages, this approach shows promise for improving outcomes in HPV-related cancers. ^{1 2 4 6 7}

Who Is on the Research Team?

Christian S Hinrichs, MD

Principal Investigator

Rutgers Cancer Institute of New Jersey

Are You a Good Fit for This Trial?

Adults over 18 with advanced HPV-related cancers (like cervical, anal, and oropharyngeal cancer) that have the HPV16 genotype. They must be in good health with proper organ function and not HIV or hepatitis positive. Women of childbearing age should use contraception and cannot be pregnant.

Inclusion Criteria

I am not pregnant or have had surgery to remove my ovaries or uterus.

I do not have HIV, hepatitis B, or active hepatitis C.

I am fully active or restricted in physically strenuous activity but can do light work.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Apheresis and Conditioning

Participants undergo apheresis to obtain T cells, followed by a non-myeloablative lymphocyte-depleting preparative regimen of cyclophosphamide and fludarabine.

1 week

Treatment

Participants receive a single infusion of E7 TCR-T cells and adjuvant high-dose aldesleukin.

1 day

Initial Follow-up

Participants are monitored for safety and tumor response, with assessments at 3 weeks and 6 weeks after treatment.

6 weeks

2 visits (in-person)

Long-term Follow-up

Participants are followed to determine 2- and 5-year disease-free survival.

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Aldesleukin
• Conditioning
• E7 TCR-T cells

Trial Overview The trial is testing E7 TCR-T cells as a pre-treatment to shrink tumors before main treatment like surgery or chemoradiation. It involves taking patients' T cells, modifying them to fight cancer, then giving them back along with aldesleukin to boost the immune system.

How Is the Trial Designed?

Group I: E7 TCR-T cells Experimental Treatment 2 Interventions

Subjects will receive a conditioning regimen, E7 TCR-T cells, and aldesleukin.

Who Is Running the Clinical Trial?

Rutgers, The State University of New Jersey

Lead Sponsor

Trials

471

Recruited

81,700+

Christian Hinrichs

Lead Sponsor

Trials

3

Recruited

70+

Iovance Biotherapeutics, Inc.

Industry Sponsor

Trials

26

Recruited

1,800+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The study successfully isolated T cell receptor (TCR) genes from HPV16E7-specific T cell clones, demonstrating the feasibility of genetically engineering CD8+ T cells to express these TCRs for potential use in adoptive immunotherapy against cervical cancer.

Transgenic T cells showed effective recognition and response to HPV16E7-specific antigens, indicating that this approach could be a promising strategy for generating targeted T cell therapies for patients with cervical cancer and other HPV16-related cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preservation and redirection of HPV16E7-specific T cell receptors for immunotherapy of cervical cancer. Scholten, KB., Schreurs, MW., Ruizendaal, JJ., et al.[2010]

T cell-mediated adoptive immunotherapy targeting HPV16 proteins E6 and E7 shows promise as a safe and effective treatment for HPV-related cancers, particularly through the generation of MHC class II-restricted T cells.

The study successfully isolated a TCR specific to HPV16-E7 from a patient with a complete response, demonstrating that TCR gene transfer can produce sufficient numbers of functional T cells that can recognize and respond to HPV-infected cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isolation and Characterization of an HLA-DRB1*04-Restricted HPV16-E7 T Cell Receptor for Cancer Immunotherapy. Mercier-Letondal, P., Marton, C., Deschamps, M., et al.[2019]

In a study involving 68 patients with HPV-associated cancers, researchers successfully reactivated and expanded T cells that specifically target HPV E6 and E7 proteins, achieving over a 1200-fold increase in T cell numbers from a significant portion of cervical and oropharyngeal cancer patients.

The presence of specific cytokines (IL-6, IL-7, IL-12, and IL-15) was crucial for the reactivation process, and the resulting T-cell lines showed promising characteristics for potential use in adoptive immunotherapy, indicating a scalable and compliant method for treating HPV16-related cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human papillomavirus type 16 E6/E7-specific cytotoxic T lymphocytes for adoptive immunotherapy of HPV-associated malignancies. Ramos, CA., Narala, N., Vyas, GM., et al.[2021]

TCR gene transfer can successfully generate HPV16 specific CD4+ T helper cells, which are crucial for effective immunotherapy against HPV-related cancers, as demonstrated through functional assays involving interferon-γ secretion and cytokine production.

The study shows that these engineered T cells can recognize specific HPV16 antigens presented by MHC molecules, indicating a promising approach for enhancing T cell responses in patients with cervical cancer and other HPV16-induced malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Generating HPV specific T helper cells for the treatment of HPV induced malignancies using TCR gene transfer. Scholten, KB., Turksma, AW., Ruizendaal, JJ., et al.[2021]

A high-avidity T cell receptor (TCR) targeting the HPV-16 E7 antigen was identified from a cervical biopsy, showing strong potential for treating HPV+ cancers due to its ability to specifically recognize and kill cancer cells.

In mouse models, T cells engineered to express this TCR successfully regressed established HPV-16+ cervical cancer tumors, paving the way for a clinical trial to evaluate this TCR gene therapy in patients with metastatic HPV+ cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineered T cells targeting E7 mediate regression of human papillomavirus cancers in a murine model. Jin, BY., Campbell, TE., Draper, LM., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02858310

Study Details | NCT02858310 | E7 TCR T Cells for Human ... Administration of T cell receptor (TCR) gene engineered T cells can induce objective tumor responses in certain malignancies including HPV-16+ cancers.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9620481/

TCR-engineered T cells targeting E7 for patients with ... We have conducted a clinical trial of E7 TCR-T cells for patients with metastatic HPV-associated cancers (NCT02858310).

3. clinicaltrial.be clinicaltrial.be/en/details/188680?per_page=20&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

E7 TCR-T Cell Immunotherapy for Human Papillomavirus ... This study will determine the tumor response rate for the treatment of HPV-associated cancers with E7 TCR-T cells. E7 TCR-T cells are autologous ...

4. insight.jci.org insight.jci.org/articles/view/99488

Engineered T cells targeting E7 mediate regression of ... It is unknown if genetically engineered TCR T cells that target E7 can mediate regression of HPV+ cancers.

5. aacrjournals.org aacrjournals.org/cancerdiscovery/article/11/5/OF15/666301/T-cell-Receptor-Engineered-T-Cells-Show-Efficacy

T-cell Receptor–Engineered T Cells Show Efficacy in HPV + ... Major Finding: A T-cell receptor T-cell therapy showed early promise in human papillomavirus (HPV)–linked cancers.

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.101

Safety and clinical activity of gene-engineered T-cell ... Conclusions: E7 TCR-T cells demonstrated safety and clinical activity in the treatment of highly refractory metastatic HPV-16+ cancers.

7. sciencedirect.com sciencedirect.com/science/article/pii/S1535610822005074

Engineered T cell therapy for viral and non-viral epithelial ... Targeting of the E7 antigen with T cell receptor (TCR)-T cells resulted in robust tumor regression in treatment-refractory cancers including ...