Evidence map›Paper›PMID 33108473›Full record

ArticleCancer immunology, immunotherapy : CII2021

PD-1 blockade synergizes with intratumoral vaccination of a therapeutic HPV protein vaccine and elicits regression of tumor in a preclinical model.

Shiwen Peng, Marietta Tan, Yen-Der Li, Max A Cheng, Emily Farmer, Louise Ferrall, Stephanie Gaillard, Richard B S Roden, Chien-Fu Hung, T-C Wu

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer immunology, immunotherapy : CII, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.2field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 36 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Shiwen Peng *Department of Pathology, The Johns Hopkins University, Baltimore, MD, USA.
Marietta Tan *Department of Otolaryngology, The Johns Hopkins University, Baltimore, MD, USA.
Yen-Der LiDepartment of Pathology, The Johns Hopkins University, Baltimore, MD, USA.
Max A ChengDepartment of Pathology, The Johns Hopkins University, Baltimore, MD, USA.
Emily FarmerDepartment of Pathology, The Johns Hopkins University, Baltimore, MD, USA.
Louise FerrallDepartment of Pathology, The Johns Hopkins University, Baltimore, MD, USA.
Stephanie GaillardOncology, The Johns Hopkins University, Baltimore, MD, USA.
Richard B S RodenDepartment of Pathology, The Johns Hopkins University, Baltimore, MD, USA.
Chien-Fu HungDepartment of Pathology, The Johns Hopkins University, Baltimore, MD, USA.
T-C WuDepartment of Pathology, The Johns Hopkins University, Baltimore, MD, USA. wutc@jhmi.edu.ORCID http://orcid.org/0000-0003-1623-4584
Johns Hopkins University · US

Funding

Treatment of HIV- and HIV+ Patients with HPV16+ CIN2/3 Using pNGLV4a-hCRTE6E7L2 DNA vaccine administered intramuscularly via electroporationP50CA098252 · NCI · JOHNS HOPKINS UNIVERSITY · PI Richard Bruce Roden · 2003 to 2026
$53.5M
Mouse modeling of HPV infectionR01CA233486 · NCI · JOHNS HOPKINS UNIVERSITY · PI HUNG, CHIEN-FU, RODEN, RICHARD BRUCE · 2019 to 2023
$3.0M
Development of Novel Spontaneous HPV Cervicovaginal Carcinoma Models for Cancer ImmunotherapyR01CA237067 · NCI · JOHNS HOPKINS UNIVERSITY · PI WU, TZYY-CHOOU · 2019 to 2023
$2.9M
Foundation for the National Institutes of Health P50CA098252Foundation for the National Institutes of Health R01CA237067NCI NIH HHS P50 CA098252NCI NIH HHS R01 CA233486NCI NIH HHS R01 CA237067
6 · The paper itself

Abstract

introductionThe human papillomavirus (HPV) encoded oncoproteins E6 and E7 are constitutively expressed in HPV-associated cancers, making them logical therapeutic targets. Intramuscular immunization of patients with HPV16 L2E7E6 fusion protein vaccine (TA-CIN) is well tolerated and induces HPV-specific cellular immune responses. Efficacy of PD-1 immune checkpoint blockade correlates with the level of tumor-infiltrating CD8 + T cells, yet most patients lack significant tumor infiltration of immune cells making immune checkpoint blockade suboptimal. We hypothesized that intratumoral vaccination with TA-CIN could increase the number of tumor-infiltrating CD8 + T cells, synergize with PD-1 blockade and result in better control of tumors compared with either PD-1 blockade or vaccination alone.

methodsWe examined the immunogenicity and antitumor effects of intratumoral vaccination with TA-CIN alone or in combination with PD-1 blockade in the TC-1 syngeneic murine tumor model expressing HPV16 E6/E7.

resultsIntratumoral vaccination with TA-CIN induced stronger antigen-specific CD8 + T cell responses and antitumor effects. Intratumoral TA-CIN vaccination generated a systemic immune response that was able to control distal TC-1 tumors. Furthermore, intratumoral TA-CIN vaccination induced tumor infiltration of antigen-specific CD8 + T cells. Knockout of Batf3 abolished antigen-specific CD8 + T cell responses and antitumor effects of intratumoral TA-CIN vaccination. Finally, PD-1 blockade synergizes with intratumoral TA-CIN vaccination resulting in significantly enhanced antigen-specific CD8 + T cell responses and complete regression of tumors, whereas either alone failed to control established TC-1 tumor.

conclusionsOur results provide rationale for future clinical testing of intratumoral TA-CIN vaccination in combination with PD-1 blockade for the control of HPV16-associated tumors.

Indexed as

AnimalsAntibodies, MonoclonalCancer VaccinesCD8-Positive T-LymphocytesFemaleImmunity, CellularLymphocytes, Tumor-InfiltratingMiceMice, Inbred C57BLPapillomavirus E7 ProteinsProgrammed Cell Death 1 ReceptorRecombinant Fusion ProteinsUterine Cervical NeoplasmsVaccinationAntibodies, MonoclonalCancer Vaccinesoncogene protein E7, Human papillomavirus type 16Papillomavirus E7 ProteinsPDCD1 protein, humanProgrammed Cell Death 1 ReceptorRecombinant Fusion ProteinsHPV-associated cancersHuman papillomavirusIntratumoralPD-1Therapeutic vaccine

Identifiers

PMID33108473
PMCPMC7979473
OpenAlexW3097515841

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.