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

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment using modified immune cells to fight cancers caused by HPV. It targets patients with specific types of cancer linked to HPV who have a certain genetic marker. The treatment works by reprogramming the patient's immune cells to attack the cancer cells.

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.

What data supports the effectiveness of the treatment 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 effectiveness in treating HPV-related cancers in humans. ^{1 2 3 4 5}

Is E7 TCR-T cell therapy safe for humans?

Research suggests that E7 TCR-T cell therapy, which targets HPV-related cancers, appears to be safe in preclinical studies, as it specifically targets cancer cells without affecting healthy tissues. However, detailed human safety data is not provided in the available studies, so further clinical trials are needed to confirm its safety in humans. ^{1 4 6 7 8}

How is the E7 TCR-T cell treatment different from other treatments for HPV-related cervical and throat 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 fight cancer. ^{1 4 8 9 10}

Research Team

Christian S Hinrichs, MD

Principal Investigator

Rutgers Cancer Institute of New Jersey

Eligibility Criteria

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

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

Treatment Details

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.

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]

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]

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]

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]

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. 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]

3. Ireland pubmed.ncbi.nlm.nih.gov

A costimulatory chimeric antigen receptor targeting TROP2 enhances the cytotoxicity of NK cells expressing a T cell receptor reactive to human papillomavirus type 16 E7. [2023]

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

Increased sensitivity of radiated murine cervical cancer tumors to E7 subunit vaccine-driven CTL-mediated killing induces synergistic anti-tumor activity. [2017]

6. 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]

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

Targeting of HPV-16+ Epithelial Cancer Cells by TCR Gene Engineered T Cells Directed against E6. [2019]

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

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

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

Expansion of Candidate HPV-Specific T Cells in the Tumor Microenvironment during Chemoradiotherapy Is Prognostic in HPV16+ Cancers. [2023]

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

Disease-stage variance in functional CD4(+) T-cell responses against novel pan-human leukocyte antigen-D region presented human papillomavirus-16 E7 epitopes. [2010]