HPV-Specific T Cell Therapy for Recurrent/Metastatic Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Tanguy Seiwert, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must be taking: Anti-PD-1, Anti-PD-L1

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Immunodeficiency, Autoimmune disease, Active infection, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

In this study, haploidentical relatives of a patient with recurrent or metastatic HPV 16-associated malignancy will be vaccinated with a therapeutic human papillomavirus (HPV) vaccine series to generate HPV-specific leukocytes. The cancer patient with recurrent or metastatic HPV16+ cancer will then be randomized to one of two arms: 1) non-myeloablative allogeneic bone marrow transplant or 2) cluster of differentiation 8 (CD8)-depleted donor lymphocyte infusion.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you should discuss your current medications with the trial team to ensure they don't interfere with the study.

What data supports the effectiveness of the treatment for HPV-specific T cell therapy for recurrent/metastatic cancer?

Research shows that HPV-specific T cell therapies, including those using engineered T cells, have demonstrated effectiveness in targeting HPV-related cancers like cervical cancer. These therapies enhance the immune system's ability to recognize and attack cancer cells, showing promise in early studies. ^{1 2 3 4 5}

Is HPV-specific T cell therapy safe for humans?

Research suggests that HPV-specific T cell therapy, including T cell receptor (TCR) gene transfer, appears to be safe for use in humans, as it has been tested in patients with HPV-related cancers without significant safety concerns. ^{1 4 5 6 7}

How is the HPV-specific T cell therapy different from other treatments for recurrent/metastatic cancer?

This treatment uses specially engineered T cells from healthy donors to target HPV-related cancers, offering a potential 'off-the-shelf' solution that can be administered without the need for a personalized approach. It aims to overcome immune rejection and enhance the body's ability to fight cancer cells, which is different from traditional therapies that may not specifically target HPV-related cancer cells. ^{1 3 5 8 9}

Research Team

Tanguy Seiwert, M.D.

Principal Investigator

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Eligibility Criteria

Adults with recurrent or metastatic HPV16+ cancers who've had platinum-based treatment, an ECOG status <2, and a haploidentical related donor. They must have tried anti-PD-1/PD-L1 therapy if indicated, measurable disease per RECIST 1.1, and adequate organ function. Exclusions include those with curable local disease options, recent immunosuppressive treatments, active autoimmune diseases or infections, pregnancy/breastfeeding without contraception use.

Inclusion Criteria

I am 18 years old or older.

aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 4 x institutional upper limit of normal

I have had at least one cycle of PD-1 or PD-L1 therapy.

Exclusion Criteria

Inability to comply with study procedures

Pregnancy or breastfeeding: females of childbearing potential must have a negative serum pregnancy test.

I have had pneumonitis treated with steroids or have it now.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Vaccination

Haploidentical relatives are vaccinated with a therapeutic HPV vaccine series to generate HPV-specific leukocytes

4 weeks

Treatment

Patients are randomized to either non-myeloablative allogeneic bone marrow transplant or CD8-depleted donor lymphocyte infusion

6 weeks

Follow-up

Participants are monitored for safety, effectiveness, and incidence of acute GVHD, with assessments at 2, 6, and 12 months

12 months

Treatment Details

Interventions

• Allogeneic HPV-specific T Cells (CAR T-cell Therapy)

Trial Overview The trial is testing the safety and effectiveness of two approaches using immune cells from vaccinated relatives: either a non-myeloablative bone marrow transplant or an infusion of CD8-depleted T cells to treat adults with HPV16+ cancers that have come back or spread.

Participant Groups

Group I: CD8-depleted donor lymphocyte infusion (DLI) per dose escalation scheme Experimental Treatment 1 Intervention

CD8-depleted donor lymphocyte infusion per dose escalation scheme from a haploidentical relative after vaccination with a therapeutic HPV vaccine series.

Group II: Allogeneic bone marrow transplant Experimental Treatment 1 Intervention

non-myeloablative allogeneic bone marrow transplant (BMT) from a haploidentical relative after vaccination with a therapeutic HPV vaccine series.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, MD

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Patients Recruited

33,600+

PapiVax Biotech, Inc.

Collaborator

Trials

6

Patients Recruited

120+

Findings from Research

The study developed HLA-A24&-E dual integrated HPV-specific cytotoxic T lymphocytes (HPV-rejTs) that can evade immune rejection while effectively suppressing cervical cancer, offering a potential 'off-the-shelf' treatment option.

Single-cell RNA sequencing revealed that these HPV-rejTs are enriched with tissue resident memory T cells, enhancing their cytotoxicity through TGFβR signaling and improved T cell receptor activation, which may lead to more effective cancer cell targeting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

iPSC-derived hypoimmunogenic tissue resident memory T cells mediate robust anti-tumor activity against cervical cancer. Furukawa, Y., Ishii, M., Ando, J., et al.[2023]

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]

Cervical cancer, primarily caused by HPV16, is linked to a weak immune response, particularly a lack of strong T-helper type 1 (Th1) immunity against HPV16 oncoproteins, which suggests that enhancing this immune response is crucial for effective treatment.

A successful protocol was developed to enrich HPV16E6-specific CD4(+) T cells from healthy donors, which could be pivotal for future adoptive T cell therapies in advanced cervical cancer, as these cells can help activate tumor-fighting mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid enrichment of human papillomavirus (HPV)-specific polyclonal T cell populations for adoptive immunotherapy of cervical cancer. de Jong, A., van der Hulst, JM., Kenter, GG., et al.[2018]

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]

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]

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]

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]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human papilloma virus-specific T cells can be generated from naïve T cells for use as an immunotherapeutic strategy for immunocompromised patients. McCormack, SE., Cruz, CRY., Wright, KE., et al.[2020]

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]

References

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

iPSC-derived hypoimmunogenic tissue resident memory T cells mediate robust anti-tumor activity against cervical cancer. [2023]

2. England pubmed.ncbi.nlm.nih.gov

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

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

Rapid enrichment of human papillomavirus (HPV)-specific polyclonal T cell populations for adoptive immunotherapy of cervical cancer. [2018]

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

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

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

T-cell Receptor-Engineered T Cells Show Efficacy in HPV+ Carcinomas. [2021]

6. 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]

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. England pubmed.ncbi.nlm.nih.gov

Human papilloma virus-specific T cells can be generated from naïve T cells for use as an immunotherapeutic strategy for immunocompromised patients. [2020]

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

Landscape of immunogenic tumor antigens in successful immunotherapy of virally induced epithelial cancer. [2021]