E7 TCR-T Cells for HPV-Related Cervical and Throat Cancer

Recruiting at 1 trial location

Overseen By Tobi Adewale

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Rutgers, The State University of New Jersey

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Active infection, Heart failure, Autoimmune, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new immunotherapy treatment using E7 TCR-T cells to target metastatic cancers related to HPV, such as cervical and throat cancers. The goal is to evaluate the effectiveness of this treatment against these cancers. Participants will receive a series of treatments, including E7 TCR-T cells and a medication called aldesleukin. This trial may suit individuals with confirmed HPV-16 related metastatic cancer who have not found success with standard therapies. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, it mentions that more than four weeks must have passed since any prior systemic therapy before receiving the E7 TCR cells, suggesting a possible need to pause certain treatments. Please consult with the trial team for specific guidance.

Is there any evidence suggesting that E7 TCR-T cells are likely to be safe for humans?

Research suggests that E7 TCR-T cell therapy shows promise for treating HPV-related cancers. In studies, these specially designed cells have found and destroyed cancer cells linked to HPV. Importantly, earlier research indicates that this treatment seems safe. It specifically targets cancer cells, protecting healthy cells.

While detailed safety information from human trials is still being collected, reaching this stage suggests some level of safety has been established. Treatments typically need to demonstrate reasonable safety in earlier trials before advancing. As more information becomes available, researchers will better understand how well people tolerate the therapy and any possible side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for HPV-related cancers?

Unlike the standard treatments for HPV-related cervical and throat cancers, which typically involve surgery, radiation, and chemotherapy, E7 TCR-T cells offer a novel approach by harnessing the power of the immune system. This treatment is unique because it involves genetically modifying a patient's own T-cells to specifically target and attack cancer cells expressing the HPV E7 protein. Researchers are excited about this therapy because it provides a more targeted attack on cancer cells, potentially reducing damage to healthy tissues and improving outcomes. Moreover, the use of aldesleukin in combination with these engineered T-cells may enhance their effectiveness, making this a promising new option in the fight against these types of cancers.

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

Research has shown that E7 TCR-T cells, which participants in this trial will receive, could be promising in treating cancers related to HPV. In studies, these specially designed cells found and destroyed cancer cells with HPV-16, a common type in these cancers. This resulted in noticeable tumor shrinkage in mice, suggesting the treatment might be effective. Additionally, trials with patients demonstrated that these cells can target and kill HPV-positive cancer cells in humans. This evidence supports the potential of E7 TCR-T cells as an effective treatment for cancers linked to HPV. ^{2 3 5 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?

This trial is for adults with metastatic or recurrent HPV-16+ cancers, including cervical, throat, penile, vulvar, vaginal, and anal cancers. They must have the HLA-A*02:01 allele and measurable disease by RECIST criteria. Participants need proper organ function and an ECOG status of 0 or 1. They should have tried standard therapy or declined it and agree to use contraception.

Inclusion Criteria

Measurable disease as assessed by RECIST Criteria Version 1.1

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

My cancer is confirmed to be HPV-16+ and has spread or not responded to treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning Regimen

Participants receive a conditioning regimen of cyclophosphamide and fludarabine

1-2 weeks

Treatment

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

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• E7 TCR-T cells

Trial Overview The trial tests E7 TCR-T cell immunotherapy in patients with HPV-associated cancers that are metastatic or resistant to treatment. It includes a conditioning regimen followed by E7 TCR-T cells infusion and aldesleukin administration to evaluate the clinical response.

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

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]

T cells engineered to target the HPV-16 E6 oncoprotein were able to specifically recognize and kill HPV-positive tumor cells, demonstrating their potential as an effective immunotherapy for HPV-associated cancers.

In a patient with metastatic anal cancer, the engineered T cells showed a significantly higher frequency of a specific T-cell clonotype in the tumor compared to peripheral blood, indicating a strong anti-tumor response that could be harnessed for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting of HPV-16+ Epithelial Cancer Cells by TCR Gene Engineered T Cells Directed against E6. Draper, LM., Kwong, ML., Gros, A., 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05686226

NCT05686226 | E7 TCR-T Cell Immunotherapy for Human ... 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 gene-engineered ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCT02858310

E7 TCR T Cells for Human Papillomavirus-Associated ... Researchers want to see if this can help people. Objective: To determine a safe dose and efficacy of E7 TCR cells and whether these cells can help patients.

3. 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).

4. withpower.com withpower.com/trial/phase-2-carcinoma-2-2023-d39bc

E7 TCR-T Cells for HPV-Related Cervical and Throat Cancer Research shows that E7 TCR-T cells can specifically recognize and kill HPV-16+ cancer cells, leading to tumor regression in a mouse model, suggesting potential ...

5. mdpi.com mdpi.com/2072-6694/16/20/3474

Potential Therapeutic Targets for the Treatment of HPV- ... Similarly, genetically engineered TCRs targeting HPV16 E7 showed efficacy in the treatment of HPV-positive uterine, cervical, anal, and head ...

6. 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.

7. 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 ...