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DRUG CLASS:

HPV-16 E6 protein inhibitor

7d
CAR-T cells based on a TCR mimic nanobody targeting HPV16 E6 exhibit antitumor activity against cervical cancer. (PubMed, Mol Ther Oncol)
Importantly, F5 CAR-T cells inhibited the growth of CaSki and SS4050 tumor xenografts in mice. These findings demonstrate that HPV-16+ cervical cancer can be targeted by F5 nanobody-based CAR-T cells, offering a valuable alternative strategy for treating HPV-16+ malignancies.
Journal • CAR T-Cell Therapy
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NFATC1 (Nuclear Factor Of Activated T Cells 1)
28d
Comparative Molecular Docking of Apigenin and Luteolin versus Conventional Ligands for TP-53, pRb, APOBEC3H, and HPV-16 E6: Potential Clinical Applications in Preventing Gynecological Malignancies. (PubMed, Curr Issues Mol Biol)
A conversion formula was applied to translate these protein-protein interaction energies to a comparable scale for non-protein interactions, further underscoring the superior binding potential of apigenin and luteolin. These findings highlight the therapeutic promise of these natural compounds in preventing HPV-16-induced oncogenesis, warranting further experimental validation for clinical applications.
Journal
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APOBEC3H (Apolipoprotein B MRNA Editing Enzyme Catalytic Subunit 3H)
1m
VGX-3100 and Electroporation in Treating Patients With HIV-Positive High-Grade Anal Lesions (clinicaltrials.gov)
P2, N=35, Active, not recruiting, AIDS Malignancy Consortium | Recruiting --> Active, not recruiting | N=80 --> 35 | Trial completion date: Sep 2029 --> Jan 2027 | Trial primary completion date: Sep 2029 --> Jan 2026
Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date • IO biomarker
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PD-L1 (Programmed death ligand 1) • CD4 (CD4 Molecule)
|
PD-L1 expression
|
bizalimogene ralaplasmid (VGX-3100)
1m
HPV16 E6-induced M2 macrophage polarization in the cervical microenvironment via exosomal miR-204-5p. (PubMed, Sci Rep)
Exosomal miR-204-5p emerges as a critical factor influencing M2 macrophage polarisation and is correlated with the severity of cervical lesions. Consequently, miR-204-5p could be used as a potential treatment and a candidate biomarker for cervical lesions.
Journal
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MIR204 (MicroRNA 204)
2ms
HPV-16 Vaccination and Pembrolizumab Plus Cisplatin for "Intermediate Risk" HPV-16-associated Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov)
P2, N=18, Active, not recruiting, Dan Zandberg | Recruiting --> Active, not recruiting | N=50 --> 18 | Trial completion date: Jun 2027 --> Jun 2026 | Trial primary completion date: Jun 2027 --> Jun 2025
Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date
|
Keytruda (pembrolizumab) • cisplatin • ISA101
2ms
Observational study on the correlation between the immune response of patients' peripheral blood stimulated by therapeutic HPV mRNA vaccine in vitro and the pathological results and clinical prognosis of patients (ChiCTR2400087487)
P=N/A, N=150, Not yet recruiting, Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine; Renji Hospital affiliated to Shanghai Jiaotong University School of Medi
New trial
|
BNT113
3ms
HPV-16 E6 mutation and viral integration related host DNA methylation implicate the development and progression of cervical cancer. (PubMed, Infect Dis (Lond))
Our study demonstrated HPV viral mutations are closely related to host gene epigenetic alterations in CC. Integration of the viral and host genetic information might be a new promising strategy for CC screening.
Journal • Epigenetic controller
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SOX17 (SRY-Box Transcription Factor 17) • ITGA4 (Integrin, alpha 4) • DLX1 (Distal-Less Homeobox 1)
4ms
New P2/3 trial • Metastases
|
Keytruda (pembrolizumab) • eseba-vec (HB-200) • HB-201
4ms
Phase II multicenter, randomized, double-blind, placebo-controlled study evaluating the efficacy of HB-200 in patients with detectable TTMV-HPV DNA after definitive treatment for HPV16 + HNSCC (ESMO 2024)
The primary objective is to assess the disease-free survival (DFS) for pts enrolled in the study receiving either HB-200 or placebo. The secondary objectives include overall survival, and safety.
P2 data • Clinical
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NavDx®
|
eseba-vec (HB-200)
5ms
Enrollment change • Trial termination • Metastases
|
CD4 (CD4 Molecule)
|
Imfinzi (durvalumab) • MEDI0457
5ms
IBRX-042 In Subjects With HPV-Associated Tumors (clinicaltrials.gov)
P1, N=12, Recruiting, ImmunityBio, Inc. | Not yet recruiting --> Recruiting | N=18 --> 12 | Trial primary completion date: Dec 2024 --> Sep 2025
Enrollment open • Enrollment change • Trial primary completion date
5ms
T-cell immunity induced and reshaped by an anti-HPV immuno-oncotherapeutic lentiviral vector. (PubMed, NPJ Vaccines)
Here, we first established that anti-vector immunity induced by Lenti-HPV-07 prime has no impact on the efficacy of a homologous boost to amplify anti-HPV T-cell immunity. We then demonstrated that the effector functions of such Lenti-HPV-07-induced T cells synergize with anti-checkpoint inhibitory treatments by systemic administration of anti-TIM3 or anti-NKG2A monoclonal antibodies. While Lenti-HPV-07 is about to enter a Phase I/IIa clinical trial, these results will help better elucidate its mode of action in immunotherapy against established HPV-mediated malignancies.
Journal • Viral vector
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CD8 (cluster of differentiation 8) • KLRC1 (Killer Cell Lectin Like Receptor C1)
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HPV-T
6ms
A Vaccine (PDS0101) Alone or in Combination With Pembrolizumab for the Treatment of Locally Advanced Human Papillomavirus-Associated Oropharynx Cancer (clinicaltrials.gov)
P1/2, N=24, Recruiting, Mayo Clinic | Trial completion date: Jul 2024 --> Jul 2025 | Trial primary completion date: Jul 2024 --> Jul 2025
Trial completion date • Trial primary completion date
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Keytruda (pembrolizumab) • Versamune HPV
6ms
VERSATILE002: Study of PDS0101 and Pembrolizumab Combination I/O in Subjects With HPV16 + Recurrent and/or Metastatic HNSCC (clinicaltrials.gov)
P2; Trial completion date: Jul 2024 --> Jun 2025 | Trial primary completion date: Jun 2024 --> Jun 2025
Trial completion date • Trial primary completion date • Metastases
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PD-L1 (Programmed death ligand 1)
|
PD-L1 expression
|
PD-L1 IHC 22C3 pharmDx
|
Keytruda (pembrolizumab) • Versamune HPV
6ms
Genetically engineered mouse model of HPV16 E6-E7 with vaginal-cervical intraepithelial neoplasia and decreased immunity. (PubMed, Heliyon)
The percentage of CD8+ T cells decreased. HPV16-E6-E7-Rosa26 induced low immune function in mice, and provides a good model for the basic research of the mechanisms of action of HPV infection-associated precancerous lesions or cervical cancer.
Preclinical • Journal
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CD8 (cluster of differentiation 8)
|
CD8 expression
7ms
A Phase 1/2 Study in Patients With HPV16+ Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma and Other Cancers (clinicaltrials.gov)
P1/2, N=200, Recruiting, Hookipa Biotech GmbH | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Mar 2024 --> Jun 2025
Trial completion date • Trial primary completion date • Metastases
|
Keytruda (pembrolizumab) • eseba-vec (HB-200) • HB-201
7ms
Dual T cell receptor/chimeric antigen receptor engineered NK-92 cells targeting the HPV16 E6 oncoprotein and the tumor-associated antigen L1CAM exhibit enhanced cytotoxicity and specificity against tumor cells. (PubMed, J Med Virol)
However, a single-signaling domain chimeric antigen receptor (ssdCAR) targeting L1CAM, a cell adhesion protein frequently overexpressed in HPV16-induced cancer, prompted a synergistic effect that significantly enhanced the cytotoxic capacity of NK-92/CD3/CD8 cells armored with both TCR and ssdCAR when both receptors simultaneously engaged their respective targets, as shown by live microscopy of 2-D and 3-D co-cultures. Thus, virus-specific TCRs from the CD8+ T cell repertoire of healthy donors can be combined with a suitable ssdCAR to enhance the cytotoxic capacity of the effector cells and, indirectly, their specificity.
Journal • Tumor cell
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CD8 (cluster of differentiation 8) • HLA-A (Major Histocompatibility Complex, Class I, A) • L1CAM (L1 cell adhesion molecule)
|
HLA-A*02
7ms
Combination of cemiplimab and ISA101b vaccine for the treatment of recurrent/metastatic HPV16 cervical cancer. (ASCO 2024)
Results from this phase 2 study of cemiplimab + ISA101b in patients with recurrent HPV16 cervical cancer show clinical benefit, especially in patients with high PD-L1 expression, and no unexpected safety signals, supporting further research.
PD(L)-1 Biomarker • IO biomarker • Metastases
|
VENTANA PD-L1 (SP263) Assay
|
Libtayo (cemiplimab-rwlc) • ISA101
7ms
Naveris Announces Launch of Phase II Clinical Study in MRD+ Head and Neck Cancer (Businesswire)
"Naveris, Inc...announced the launch of a Phase II clinical study in minimal residual disease positive (MRD+) HPV-driven head and neck cancer. The study will be led by Memorial Sloan Kettering Cancer Center (MSKCC), a top cancer treatment and research institution. The primary objective of this multicenter randomized study is to evaluate the efficacy of HB-200, a novel intervention, for patients with HPV16+ head and neck squamous cell cancer (HNSCC) with molecular relapse, defined as the presence of circulating Tumor Tissue Modified Viral (TTMV)-HPV DNA without clinical or radiographic evidence of recurrence following definitive treatment."
Trial status
|
NavDx®
|
eseba-vec (HB-200)
7ms
New P2 trial
|
eseba-vec (HB-200) • HB-201
7ms
HPV16 E6 TCR T Cells for Cervical Carcinoma (clinicaltrials.gov)
P1/2, N=18, Recruiting, TCRCure Biopharma Ltd. | Trial completion date: Aug 2024 --> Aug 2025 | Trial primary completion date: Dec 2023 --> Dec 2024
Trial completion date • Trial primary completion date • Metastases
|
HLA-A2 positive
|
cyclophosphamide • fludarabine IV
8ms
CRTE7A2-01 TCR-T Cells for HPV-16 Positive Advanced Cancers (clinicaltrials.gov)
P1, N=24, Not yet recruiting, Corregene Biotechnology Co., Ltd
New P1 trial • Metastases
|
cyclophosphamide • CRTE7A2-01
8ms
Phase Ib/II of TG4001 and Avelumab in HPV16 Positive R/M Cancers (clinicaltrials.gov)
P1/2, N=150, Active, not recruiting, Transgene | Recruiting --> Active, not recruiting | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2024
Enrollment closed • Trial completion date • Trial primary completion date • Metastases
|
Bavencio (avelumab) • tipapkinogene sovacivec (TG4001)
8ms
IBRX-042 In Subjects With HPV-Associated Tumors (clinicaltrials.gov)
P1, N=18, Not yet recruiting, ImmunityBio, Inc. | Initiation date: Mar 2024 --> Jun 2024
Trial initiation date
9ms
COMMANDER-001: Study of SQZ-eAPC-HPV in Patients With HPV16+ Recurrent, Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
P1/2, N=20, Terminated, SQZ Biotechnologies | N=60 --> 20 | Trial completion date: Mar 2024 --> Nov 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Mar 2024 --> Nov 2023; Corporate Decision
Enrollment change • Trial completion date • Trial termination • Trial primary completion date • Combination therapy • Checkpoint inhibition • Metastases
|
Keytruda (pembrolizumab)
9ms
Evaluation of the anti-cancer efficacy of lipid nanoparticles containing siRNA against HPV16 E6/E7 combined with cisplatin in a xenograft model of cervical cancer. (PubMed, PLoS One)
The combination of ENB101-LNP, which inhibits E6/E7 of HPV 16, with cisplatin, demonstrated significant anticancer activity in the xenograft mouse model of cervical cancer.
Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • HLA-A (Major Histocompatibility Complex, Class I, A) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
|
cisplatin
10ms
HARE-40: HPV Anti-CD40 RNA vaccinE (clinicaltrials.gov)
P1/2, N=32, Completed, University of Southampton | Active, not recruiting --> Completed
Trial completion
|
BNT113
10ms
HPV16 E6 Oncogene Contributes to Cancer Immune Evasion by Regulating PD-L1 Expression through a miR-143/HIF-1a Pathway. (PubMed, Viruses)
According to our results, in the E6 knock out (E6KO) cell lines an increased expression of miR-143 was recorded, while a decrease in the expression of HIF-1a and PD-L1 was exhibited. These findings indicate that E6 protein probably plays a significant role in enabling cervical cancer cells to evade the immune system, while we propose a molecular pathway in cervical cancer, where PD-L1's expression is regulated by E6 protein through a miR-143/HIF-1a axis.
Journal • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • MIR143 (MicroRNA 143)
|
PD-L1 expression • HIF1A expression
10ms
A Vaccine (PDS0101) and Chemoradiation for the Treatment of Stage IB3-IVA Cervical Cancer, the IMMUNOCERV Trial (clinicaltrials.gov)
P2, N=22, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=35 --> 22 | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Mar 2025
Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date • Metastases
|
ALK (Anaplastic lymphoma kinase)
|
cisplatin • Versamune HPV
10ms
ProcemISA: A Phase II Study of Cemiplimab and ISA101b in Patients With Recurrent/Metastatic HPV16 Positive OPC (clinicaltrials.gov)
P2, N=65, Active, not recruiting, ISA Pharmaceuticals | Recruiting --> Active, not recruiting | Trial primary completion date: Dec 2023 --> Jun 2024
Enrollment closed • Trial primary completion date • Metastases
|
Libtayo (cemiplimab-rwlc) • ISA101
10ms
Autologous T Cells Targeting HPV16 HPV18 & Survivin in Patients With R/R HPV-related Oropharyngeal Cancers (clinicaltrials.gov)
P1, N=36, Not yet recruiting, NexImmune Inc. | Trial completion date: Aug 2025 --> Aug 2027 | Trial primary completion date: Jul 2024 --> Jul 2026
Trial completion date • Trial primary completion date
|
HLA-A (Major Histocompatibility Complex, Class I, A)
|
cyclophosphamide • fludarabine IV • NEXI-003
11ms
HPV16 E6 promoting cervical cancer progression through down-regulation of miR-320a to increase TOP2A expression. (PubMed, Cancer Med)
We confirmed that HPV16 E6 promoted the TOP2A expression through down-regulation of miR-320a, thus promoting CC development, and the HPV16 E6/miR-320a/TOP2A axis may perform as a potential target for CC treatment.
Journal
|
TOP2A (DNA topoisomerase 2-alpha) • MIR320A (MicroRNA 320a)
11ms
OpcemISA: A Randomized Phase 2 Study of Cemiplimab ± ISA101b in HPV16-Positive OPC (clinicaltrials.gov)
P2, N=194, Active, not recruiting, ISA Pharmaceuticals | Trial completion date: Dec 2024 --> Jun 2025 | Trial primary completion date: Sep 2023 --> Sep 2024
Trial completion date • Trial primary completion date
|
PD-L1 (Programmed death ligand 1)
|
PD-L1 expression
|
Libtayo (cemiplimab-rwlc) • ISA101
11ms
A Study HB-201 in Patients With Newly Diagnosed HPV16+ Oropharynx or Locally Advanced Cervical Cancer (clinicaltrials.gov)
P1, N=10, Terminated, Hookipa Biotech GmbH | N=27 --> 10 | Recruiting --> Terminated; Sponsor decision.
Enrollment change • Trial completion date • Trial termination • Trial primary completion date • Metastases
|
HB-201
11ms
Preferential Expansion of HPV16 E1-Specific T Cells from Healthy Donors' PBMCs after Ex Vivo Immunization with an E1E2E6E7 Fusion Antigen. (PubMed, Cancers (Basel))
Therapeutic HPV vaccines in clinical development show great promise in improving outcomes for patients who mount an anti-HPV T-cell response; however, far from all patients elicit a sufficient immunological response...We suggest that this assay can be a valuable translational tool to complement the known animal models, not only for HPV therapeutic vaccines, and supports the use of E1 as an immunotherapeutic target. Nevertheless, the findings reported here need to be validated in a larger number of donors and preferably in patient samples.
Preclinical • Journal
|
TRIP13 (Thyroid Hormone Receptor Interactor 13)
|
HPV-T
11ms
Trial completion date • Trial primary completion date • Combination therapy • Metastases
|
PD-L1 (Programmed death ligand 1)
|
Keytruda (pembrolizumab) • BNT113
11ms
Trial completion date • Trial primary completion date • Metastases
|
Keytruda (pembrolizumab) • eseba-vec (HB-200) • HB-201
12ms
HPV16 E6/E7-mediated regulation of PiwiL1 expression induces tumorigenesis in cervical cancer cells. (PubMed, Cell Oncol (Dordr))
Our study demonstrates that PiwiL1 act as an oncogene in cervical cancer by inducing tumor-associated properties and EMT pathway. The finding that HPV oncogenes, E6/E7 can positively regulate PiwiL1 suggests a possible mechanism behind HPV-mediated tumorigenesis in cervical cancer.
Journal
|
E2F1 (E2F transcription factor 1)
12ms
HPV16 E6 TCR T Cells for Cervical Carcinoma (clinicaltrials.gov)
P1/2, N=18, Recruiting, TCRCure Biopharma Ltd. | Trial primary completion date: Mar 2023 --> Dec 2023
Trial primary completion date • Metastases
|
HLA-A2 positive
|
cyclophosphamide • fludarabine IV
1year
COMMANDER-001: Study of SQZ-eAPC-HPV in Patients With HPV16+ Recurrent, Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
P1/2, N=60, Active, not recruiting, SQZ Biotechnologies | Recruiting --> Active, not recruiting
Enrollment closed • Combination therapy • Checkpoint inhibition • Metastases
|
Keytruda (pembrolizumab)
1year
HPV Circulating Cell-Free DNA Kinetics in Cervical Cancer Patients Undergoing Definitive Chemoradiation. (PubMed, Int J Radiat Oncol Biol Phys)
"Forty-seven patients with cervical cancer were enrolled on this study between 2017 and 2022, either as part of a standard-of-care (SOC) treatment banking protocol (33 patients) or as part of a clinical trial combining a therapeutic HPV vaccine (PDS0101; Immunocerv, 14 patients)...Treatment with a therapeutic HPV vaccine was associated with a more rapid decline in cfHPV DNA. Further analysis of cfDNA kinetics could provide valuable information on the relationship between cfDNA levels, treatment response, and clinical outcomes."
Journal
|
AmpFire HPV Assay
|
Versamune HPV
1year
Characterization of tumor specific CD8+ T cell responses in patients with recurrent/metastatic HPV16-positive head and neck cancer receiving HB-200 monotherapy as second or later line treatment in a phase 1 study (SITC 2023)
HB-200 is comprised of an alternating sequence of two replicating attenuated arenavirus vectors derived from LCMV (HB-201) and Pichinde virus (HB-202), respectively, expressing the same non-oncogenic HPV16 E7E6 fusion protein. Conclusions HB-200 monotherapy induces promising HPV16+ tumor-specific T cell responses and tumor infiltration in heavily pre-treated patients. This immune response coupled with clinical benefit in monotherapy suggests that HB-200 may enhance and strengthen current immunotherapy approaches by targeting specific tumor antigens.
Clinical • P1 data • Metastases
|
CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma)
|
eseba-vec (HB-200) • HB-201