Evidence map›Paper›PMID 37434263›Full record

ArticleJournal of experimental & clinical cancer research : CR2023

rWTC-MBTA: autologous vaccine prevents metastases via antitumor immune responses.

Juan Ye, Herui Wang, Rogelio Medina, Samik Chakraborty, Mitchell Sun, Alex Valenzuela, Xueyu Sang, Yaping Zhang, Ondrej Uher, Jan Zenka and 2 more

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

Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

10 citing papers in PubMed, 12 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

12 authors at 2 institutions in 2 countries.

Juan Ye *Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 37, Room 1000 37 Convent Dr, Bethesda, MD, 20892, USA.
Herui Wang *Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 37, Room 1000 37 Convent Dr, Bethesda, MD, 20892, USA.
Rogelio MedinaNeuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 37, Room 1000 37 Convent Dr, Bethesda, MD, 20892, USA.
Samik ChakrabortyNE1 Inc, New York, NY, USA.
Mitchell SunNeuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 37, Room 1000 37 Convent Dr, Bethesda, MD, 20892, USA.
Alex ValenzuelaNeuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 37, Room 1000 37 Convent Dr, Bethesda, MD, 20892, USA.
Xueyu SangNeuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 37, Room 1000 37 Convent Dr, Bethesda, MD, 20892, USA.
Yaping ZhangNeuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 37, Room 1000 37 Convent Dr, Bethesda, MD, 20892, USA.
Ondrej UherSection on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Jan ZenkaDepartment of Medical Biology, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic.
Karel PacakSection on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Zhengping ZhuangNeuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 37, Room 1000 37 Convent Dr, Bethesda, MD, 20892, USA. zhengping.zhuang@nih.gov.ORCID http://orcid.org/0000-0002-0009-7370
National Institutes of Health · USUniversity of South Bohemia in České Budějovice · CZ

Funding

Hypoxia signaling in cancer developmentZIABC011773 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI ZHUANG, ZHENGPING · 2017 to 2025
$13.0M
6 · The paper itself

Abstract

backgroundAutologous tumor cell-based vaccines (ATVs) aim to prevent and treat tumor metastasis by activating patient-specific tumor antigens to induce immune memory. However, their clinical efficacy is limited. Mannan-BAM (MB), a pathogen-associated molecular pattern (PAMP), can coordinate an innate immune response that recognizes and eliminates mannan-BAM-labeled tumor cells. TLR agonists and anti-CD40 antibodies (TA) can enhance the immune response by activating antigen-presenting cells (APCs) to present tumor antigens to the adaptive immune system. In this study, we investigated the efficacy and mechanism of action of rWTC-MBTA, an autologous whole tumor cell vaccine consisting of irradiated tumor cells (rWTC) pulsed with mannan-BAM, TLR agonists, and anti-CD40 antibody (MBTA), in preventing tumor metastasis in multiple animal models.

methodsThe efficacy of the rWTC-MBTA vaccine was evaluated in mice using breast (4T1) and melanoma (B16-F10) tumor models via subcutaneous and intravenous injection of tumor cells to induce metastasis. The vaccine's effect was also assessed in a postoperative breast tumor model (4T1) and tested in autologous and allogeneic syngeneic breast tumor models (4T1 and EMT6). Mechanistic investigations included immunohistochemistry, immunophenotyping analysis, ELISA, tumor-specific cytotoxicity testing, and T-cell depletion experiments. Biochemistry testing and histopathology of major tissues in vaccinated mice were also evaluated for potential systemic toxicity of the vaccine.

resultsThe rWTC-MBTA vaccine effectively prevented metastasis and inhibited tumor growth in breast tumor and melanoma metastatic animal models. It also prevented tumor metastasis and prolonged survival in the postoperative breast tumor animal model. Cross-vaccination experiments revealed that the rWTC-MBTA vaccine prevented autologous tumor growth, but not allogeneic tumor growth. Mechanistic data demonstrated that the vaccine increased the percentage of antigen-presenting cells, induced effector and central memory cells, and enhanced CD4

conclusionThe rWTC-MBTA vaccine demonstrated efficacy in multiple animal models through T-cell mediated cytotoxicity and has potential as a therapeutic option for preventing and treating tumor metastasis with minimal systemic toxicity.

Indexed as

Breast NeoplasmsCancer VaccinesMelanomaAnimalsAntigens, NeoplasmCD40 AntigensFemaleHumansImmunologic MemoryMannansMiceAntigens, NeoplasmCancer VaccinesCD40 AntigensMannansMannan-BAMMetastasisrWTC-MBTA vaccineT-cell cytotoxicityTLR agonists

Identifiers

PMID37434263
PMCPMC10337177
OpenAlexW4383999224

What OpenQuestion holds

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LicenceCC BY
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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.