HPV Specific T Cells + Immunotherapy for Cancer

(HESTIA Trial)

Overseen By Carlos Ramos, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Baylor College of Medicine

Must not be taking: Tumor vaccines, T cell antibodies

Disqualifiers: HIV, Severe infection, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment using special immune cells called HPVST cells to combat cancers linked to the human papillomavirus (HPV). Researchers aim to determine if these cells can survive in the body and shrink tumors. If the first part of the trial proves safe, a second group will receive HPVST cells along with Nivolumab, an immunotherapy that enhances the immune system's ability to fight cancer. This study seeks individuals with HPV-related cancers that have returned or not responded to other treatments. Participants must have their cancer confirmed as HPV-linked through a biopsy. As a Phase 1 trial, this 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, you cannot participate if you are currently receiving any investigational agents or have received tumor vaccines or T cell antibodies in the past 4 weeks.

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

In a previous study, researchers found that using T cells to target cancer cells infected with HPV showed promising results. These special T cells, taken from patients' blood, boosted the body's immune response against the virus, indicating their potential to fight cancer. However, because this is a new approach, limited information exists about possible side effects.

For the combination treatment with HPV-specific T cells and Nivolumab, it is important to note that the FDA has already approved Nivolumab for some cancers, demonstrating its safety for those conditions. When combined with T cells, the goal is to further strengthen the immune system. Early research suggests this combination could be effective, but complete safety data for this specific mix is not yet available.

In summary, while early findings are encouraging, detailed safety information is still being collected. This trial represents one of the first steps to ensure these treatments are safe for everyone. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about HPV Specific T Cells for cancer treatment because they offer a targeted approach by harnessing the body's immune system to fight HPV-related cancers. Unlike traditional treatments like chemotherapy, which attacks both healthy and cancerous cells, this therapy utilizes HPV-specific T cells to directly target and destroy cancerous cells associated with the human papillomavirus. Additionally, in one arm of the treatment, the combination with lymphodepletion and nivolumab—a type of immunotherapy—aims to enhance the immune response by creating an environment where these T cells can work more effectively. This promising approach not only aims to improve treatment precision but also to reduce side effects by sparing healthy cells.

What evidence suggests that this trial's treatments could be effective for HPV-associated cancers?

Research has shown that special immune cells called HPV-specific T cells can effectively fight cancers linked to the HPV virus. These cells target and destroy virus-infected cells, helping the body manage the cancer. Studies have demonstrated promising results in patients, with signs of improved survival rates. In this trial, participants in Group A will receive HPV-specific T cells alone.

In Group B, participants will receive a combination treatment that includes HPV-specific T cells, lymphodepletion with Cytoxan and Fludarabine, and Nivolumab, a type of antibody therapy. Adding Nivolumab may boost the immune response against cancer. Nivolumab enhances T cell function by blocking a protein that prevents them from attacking the cancer. Early evidence suggests this combination could control tumors more effectively than using HPV-specific T cells alone. ^{1 6 7 8 9}

Who Is on the Research Team?

Carlos Ramos, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for adults over 18 with recurrent or persistent HPV-associated cancers after standard treatment, or those who can't receive standard therapy. Participants need a Karnofsky score of at least 50%, indicating they are able to perform daily activities. They must have a life expectancy of more than 6 weeks, adequate organ function, and agree to use effective birth control. People with HIV, current investigational treatments, severe infections, or who are pregnant cannot join.

Inclusion Criteria

I am able to care for myself but cannot do normal activities or work.

Life expectancy ≥ 6 weeks.

Bilirubin < 3 × upper limit of normal (ULN), AST < 5 × ULN, Hgb ≥ 7.0 g/dL

Exclusion Criteria

I am not currently on experimental drugs or had cancer vaccines or T cell treatments in the last 4 weeks.

Pregnancy or lactation.

I do not have a severe ongoing infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive HPV-specific T cells, with potential additional doses based on response; Group B may receive additional nivolumab and lymphodepletion

6 weeks

Initial infusion on day 0, potential additional doses based on response; Group B receives nivolumab every 2 weeks for 4 doses

Follow-up

Participants are monitored for safety and effectiveness after treatment, including blood draws and examinations

6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cytoxan
• Fludarabine
• HPV Specific T Cells
• Nivolumab

Trial Overview The study tests HPV-specific T cells (HPVST) designed to fight cancer by targeting the virus that causes it. The first group receives only these cells; if safe, another group will get them plus Nivolumab—an FDA-approved antibody—in a lymphodepleted state to potentially enhance effectiveness.

How Is the Trial Designed?

Group I: Group B Experimental Treatment 4 Interventions

HPV Specific T Cells plus lymphodepletion (Cytoxan and Fludarabine) and nivolumab

Group II: Group A Experimental Treatment 1 Intervention

HPV Specific T Cells

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials

114

Recruited

2,900+

The Methodist Hospital Research Institute

Collaborator

Trials

299

Recruited

82,500+

Published Research Related to This Trial

The TCRα-modified T cell product showed no signs of tumorigenic or mutagenic activity in vitro, indicating that the viral vectors used for its generation are safe and do not cause genetic damage.

In mouse models, the adoptive transfer of TCRα-engineered T cells did not disrupt normal body functions and showed no acute toxicity or harmful immune reactions, suggesting a favorable safety profile for potential clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of the mouse TCRα - transduced T cell product in preclinical models in vivo and in vitro. Kalinina, A., Bruter, A., Persiyantseva, N., et al.[2022]

In a study of patients with metastatic cervical cancer, the most effective T cell responses were found to target mutated neoantigens and a cancer germline antigen, rather than the expected viral antigens from human papillomavirus (HPV).

The presence of T cells targeting both viral and nonviral antigens in the PD-1-expressing compartment indicates that blocking PD-1 could enhance the effectiveness of immunotherapy by activating a broader range of antitumor T cell responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Landscape of immunogenic tumor antigens in successful immunotherapy of virally induced epithelial cancer. Stevanović, S., Pasetto, A., Helman, SR., et al.[2021]

A T-cell receptor therapy has shown early effectiveness in treating cancers associated with human papillomavirus (HPV), indicating a potential new approach for these types of cancers.

This therapy targets specific T-cells to fight HPV-linked cancers, suggesting a mechanism that could enhance the immune response against these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cell Receptor-Engineered T Cells Show Efficacy in HPV+ Carcinomas. [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]

Anti-CTLA4 and anti-PD1/PD-L1 immunotherapies represent a significant shift in cancer treatment by enhancing the immune system's ability to fight tumors rather than directly targeting the tumor cells themselves.

These immunotherapies can lead to unique immune-related adverse events due to the activation of the immune system against normal tissues, necessitating changes in clinical management to address potential autoimmune reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Management of adverse events associated with cancer immunotherapy]. Champiat, S., Michot, JM., Lambotte, O.[2019]

Cancer immunotherapies, particularly anti-CTLA4 and anti-PD1/PD-L1, are becoming more common in treatment regimens, leading to increased exposure of patients to immune-related adverse events (irAEs).

These immunotherapies can activate the immune system to fight tumors effectively, but they also have a unique toxicity profile that can cause autoimmune reactions, necessitating changes in clinical management practices to address these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Management of adverse events associated with cancer immunotherapy]. Laparra, A., Champiat, S., Michot, JM., 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]

Engineered T cell therapies, like CAR T cells and TCR T cell therapies, have shown remarkable efficacy in treating certain blood cancers, highlighting their potential as a powerful tool in cancer immunotherapy.

However, these therapies also pose unique safety challenges, such as cytokine release syndrome and neurotoxicity, which require careful nonclinical safety assessments to ensure patient safety during development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonclinical safety assessment of engineered T cell therapies. Lebrec, H., Maier, CC., Maki, K., 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11843463/

Novel Combination Immunotherapy and Clinical Activity in ... This trial identified a population of patients with HPV-associated cancer with promising antitumor responses and improved survival, supporting ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6731765/

HPV-specific T-cells can be generated from naïve ... As EBV-specific T-cells have been highly successful in treating or preventing EBV-associated tumors, we hypothesized that the development of a manufacturing ...

3. jitc.bmj.com jitc.bmj.com/content/12/6/e008667

Single-cell analysis reveals cellular and molecular factors ... Single-cell transcriptome analysis suggested that the clinical benefit of HPV infection was voided by the heterogeneity of malignant cells.

4. onclive.com onclive.com/view/immunotherapy-outcomes-in-hpv-associated-head-and-neck-cancer-fuel-investigative-efforts

Immunotherapy Outcomes in HPV-Associated Head and ... Promising data from studies evaluating immunotherapy and cellular therapy for patients with head and neck cancers associated with human papilloma virus (HPV)

5. rupress.org rupress.org/jem/article/217/10/e20200389/151975/Profiling-HPV-16-specific-T-cell-responses-reveals

Profiling HPV-16–specific T cell responses reveals broad ... Virus-specific T cells have been shown to play an important role in remission of HPV-associated cancers, and immunodeficiency correlates with ...

6. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2830546

Novel Combination Immunotherapy and Clinical Activity in ... This trial identified a population of patients with HPV-associated cancer with promising antitumor responses and improved survival.

7. nature.com nature.com/articles/s41541-024-00894-0

T-cell immunity induced and reshaped by an anti-HPV ... The immunity induced by Lenti-HPV-07 is long-lasting and completely prevents tumor relapse. We showed that the T cells induced by this vaccine ...

8. jitc.bmj.com jitc.bmj.com/content/9/Suppl_2/A513.responses

483 Initial safety results and immune responses induced by ... T-cells targeting HPV-16 and/or HPV-18 were increased after vaccination in 100% of patients, with 3/6 (50%) developing HPV-16 T cells and 5/6 ( ...

9. cancer.gov cancer.gov/about-cancer/causes-prevention/risk/infectious-agents/hpv-and-cancer

HPV and Cancer - NCI Key facts about the efficacy and safety of the HPV vaccine: The HPV vaccine is estimated to prevent up to 90% of cancers caused by HPV infection ...