E7 TCR-T Cells for HPV-Related Cancer

Recruiting at 1 trial location

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

Trial Summary

What is the purpose of this trial?

The goal of this study is to determine the feasibility of administration of a single dose of E7 TCR-T cells as induction therapy prior to definitive treatment (chemoradiation or surgery) of locoregionally advanced HPV-associated cancers. The intent of E7 TCR-T cell treatment is to shrink or eliminate tumors and thereby facilitate definitive therapy and increase overall survival. This study seeks to determine 1) if E7 TCR-T cells can be administered without undue delay in definitive treatment, 2) the tumor response rate to E7 TCR-T cell treatment, and 3) the disease-free survival rate at 2 and 5 years. Participants will undergo an apheresis procedure to obtain T cells that will be genetically engineered to generate E7 TCR-T cells. They will receive a conditioning regimen, a single infusion of their own E7 TCR-T cells, and adjuvant aldesleukin. Participants will follow up to assess safety and determine tumor response and will return to their primary oncology team for definitive 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.

What data supports the effectiveness of the E7 TCR-T Cells treatment for HPV-related cancer?

Research shows that engineered T cells targeting the E7 protein of HPV can effectively recognize and kill HPV-positive cancer cells in lab settings and animal models. This suggests that the treatment could potentially help in reducing HPV-related cancers in humans. ^{1 2 3 4 5}

Is E7 TCR-T cell therapy safe for humans?

The research suggests that E7 TCR-T cell therapy, which targets HPV-related cancers, appears to be safe in preclinical models, as it specifically targets cancer cells without affecting healthy tissues. However, detailed human safety data is not provided in the available studies. ^{1 2 3 4 6}

How is the E7 TCR-T cell treatment different from other treatments for HPV-related cancer?

The E7 TCR-T cell treatment is unique because it uses genetically engineered T cells to specifically target and kill cancer cells expressing the HPV E7 protein, which is not found in healthy tissues. This approach is different from traditional treatments as it involves modifying the patient's own immune cells to enhance their ability to recognize and attack HPV-related cancer cells. ^{1 2 4 6 7}

Research Team

Christian S Hinrichs, MD

Principal Investigator

Rutgers Cancer Institute of New Jersey

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

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

Engineered T cells targeting E7 mediate regression of human papillomavirus cancers in a murine model. [2022]

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

Human papillomavirus type 16 E6/E7-specific cytotoxic T lymphocytes for adoptive immunotherapy of HPV-associated malignancies. [2021]

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

Preservation and redirection of HPV16E7-specific T cell receptors for immunotherapy of cervical cancer. [2010]

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

Isolation and Characterization of an HLA-DRB1*04-Restricted HPV16-E7 T Cell Receptor for Cancer Immunotherapy. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Increase of human papillomavirus-16 E7-specific T helper type 1 response in peripheral blood of cervical cancer patients after radiotherapy. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Generating HPV specific T helper cells for the treatment of HPV induced malignancies using TCR gene transfer. [2021]

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

An unexpectedly large polyclonal repertoire of HPV-specific T cells is poised for action in patients with cervical cancer. [2023]