Microbial-Based Cancer Therapies

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (15 September 2022) | Viewed by 10449

Special Issue Editors

Division of Hematology, Oncology and Cell Therapy, Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA
Interests: microbial-based cancer therapies (MBCTs); tumor microbiome; immune-reconstituted patient-derived xenograft (AIR-PDX) mouse models; cancer immuno-nanoparticles
Department of Internal Medicine, Section of Hematology, Oncology, and Cell Therapy, Rush University Medical Center, Chicago, IL 60612, USA
Interests: immune system; tumor microenvironment; engaging host immune responses with novel approaches to eliminate cancer

Special Issue Information

Dear Colleagues,

Microbial-based cancer therapies (MBCTs) have been shown to augment anti-tumor immune responses and improve long-term clinical outcomes. Although reported successes extend across millennia and involve a spectrum of microbial species, the number of MBCTs that have been granted federal approval remain limited. Thus, there is great need for expanding awareness regarding MBCTs. Thus far, major mechanisms involve 1) debulking of the cancer via preferential tumor cell (versus normal cell) lysis by oncolytic pathogens and 2) conversion of the tumor microenvironment from “cold” (immune response-preventing) to “hot” (anti-tumor immunity-augmenting) by oncolytic and non-oncolytic pathogens, both active and inactivated. However, much more is to be gained from further studies and, thus, the need for a Special Issue covering the spectrum of MBCT-related discoveries from basic mechanisms to translational avenues, case studies, and clinical successes as an innovative means of improving and saving the lives of patients with cancer.

Dr. Andrew Zloza
Dr. Amanda L. Marzo
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cancer
  • immunotherapy
  • tumor
  • immuno-oncology
  • microbial-based cancer therapies (MBCTs)
  • tumor microbiome
  • virus
  • viral
  • bacteria
  • bacterial
  • oncolytic
  • non-oncolytic

Published Papers (3 papers)

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Research

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18 pages, 3781 KiB  
Article
Intestinal Microbiota Influence Doxorubicin Responsiveness in Triple-Negative Breast Cancer
by Alaa Bawaneh, Adam S. Wilson, Nicole Levi, Marissa M. Howard-McNatt, Akiko Chiba, David R. Soto-Pantoja and Katherine L. Cook
Cancers 2022, 14(19), 4849; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14194849 - 04 Oct 2022
Cited by 16 | Viewed by 3179
Abstract
Triple-negative breast cancer (TNBC) is highly aggressive with a poor 5-year survival rate. Targeted therapy options are limited and most TNBC patients are treated with chemotherapy. This study aimed to determine whether doxorubicin (Dox) shifts the gut microbiome and whether gut microbiome populations [...] Read more.
Triple-negative breast cancer (TNBC) is highly aggressive with a poor 5-year survival rate. Targeted therapy options are limited and most TNBC patients are treated with chemotherapy. This study aimed to determine whether doxorubicin (Dox) shifts the gut microbiome and whether gut microbiome populations influence chemotherapeutic responsiveness. Female BALB/c mice (n = 115) were injected with 4T1-luciferase cells (a murine syngeneic TNBC model) and treated with Dox and/or antibiotics, high-fat diet-derived fecal microbiota transplant (HFD-FMT), or exogenous lipopolysaccharide (LPS). Metagenomic sequencing was performed on fecal DNA samples. Mice that received Dox were stratified into Dox responders or Dox nonresponders. Mice from the Dox responders and antibiotics + Dox groups displayed reduced tumor weight and metastatic burden. Metagenomic analysis showed that Dox was associated with increased Akkermansia muciniphila proportional abundance. Moreover, Dox responders showed an elevated proportional abundance of Akkermansia muciniphila prior to Dox treatment. HFD-FMT potentiated tumor growth and decreased Dox responsiveness. Indeed, lipopolysaccharide, a structural component of Gram-negative bacteria, was increased in the plasma of Dox nonresponders and FMT + Dox mice. Treatment with exogenous LPS increases intestinal inflammation, reduces Dox responsiveness, and increases lung metastasis. Taken together, we show that modulating the gut microbiota through antibiotics, HFD-FMT, or by administering LPS influenced TNBC chemotherapy responsiveness, lung metastasis, and intestinal inflammation. Full article
(This article belongs to the Special Issue Microbial-Based Cancer Therapies)
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25 pages, 6609 KiB  
Article
The Anti-Tumor Effect of Lactococcus lactis Bacteria-Secreting Human Soluble TRAIL Can Be Enhanced by Metformin Both In Vitro and In Vivo in a Mouse Model of Human Colorectal Cancer
by Katarzyna Kaczmarek, Jerzy Więckiewicz, Kazimierz Węglarczyk, Maciej Siedlar and Jarek Baran
Cancers 2021, 13(12), 3004; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13123004 - 15 Jun 2021
Cited by 3 | Viewed by 2731
Abstract
Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) induces apoptosis of many cancer cells, including CRC cells, being non-harmful for normal ones. However, recombinant form of human TRAIL failed in clinical trial when administered intravenously. To assess the importance of TRAIL in CRC patients, new [...] Read more.
Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) induces apoptosis of many cancer cells, including CRC cells, being non-harmful for normal ones. However, recombinant form of human TRAIL failed in clinical trial when administered intravenously. To assess the importance of TRAIL in CRC patients, new form of TRAIL delivery would be required. Here we used genetically modified, non-pathogenic Lactococcus lactis bacteria as a vehicle for local delivery of human soluble TRAIL (hsTRAIL) in CRC. Operating under the Nisin Controlled Gene Expression System (NICE), the modified bacteria (L. lactis(hsTRAIL+)) were able to induce cell death of HCT116 and SW480 human cancer cells and reduce the growth of HCT116-tumor spheres in vitro. This effect was cancer cell specific as the cells of normal colon epithelium (FHC cells) were not affected by hsTRAIL-producing bacteria. Metformin (MetF), 5-fluorouracil (5-FU) and irinotecan (CPT-11) enhanced the anti-tumor actions of hsTRAIL in vitro. In the NOD-SCID mouse model, treatment of subcutaneous HCT116-tumors with L. lactis(hsTRAIL+) bacteria given intratumorally, significantly reduced the tumor growth. This anti-tumor activity of hsTRAIL in vivo was further enhanced by oral administration of MetF. These findings indicate that L. lactis bacteria could be suitable for local delivery of biologically active human proteins. At the same time, we documented that anti-tumor activity of hsTRAIL in experimental therapy of CRC can be further enhanced by MetF given orally, opening a venue for alternative CRC-treatment strategies. Full article
(This article belongs to the Special Issue Microbial-Based Cancer Therapies)
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Review

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31 pages, 1325 KiB  
Review
Recombinant Attenuated Salmonella enterica as a Delivery System of Heterologous Molecules in Cancer Therapy
by Elayne Irene Becerra-Báez, Sergio Enrique Meza-Toledo, Paola Muñoz-López, Luis Fernando Flores-Martínez, Karla Fraga-Pérez, Kevin Jorge Magaño-Bocanegra, Uriel Juárez-Hernández, Armando Alfredo Mateos-Chávez and Rosendo Luria-Pérez
Cancers 2022, 14(17), 4224; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14174224 - 30 Aug 2022
Cited by 10 | Viewed by 3759
Abstract
Over a century ago, bacterial extracts were found to be useful in cancer therapy, but this treatment modality was obviated for decades. Currently, in spite of the development and advances in chemotherapies and radiotherapy, failure of these conventional treatments still represents a major [...] Read more.
Over a century ago, bacterial extracts were found to be useful in cancer therapy, but this treatment modality was obviated for decades. Currently, in spite of the development and advances in chemotherapies and radiotherapy, failure of these conventional treatments still represents a major issue in the complete eradication of tumor cells and has led to renewed approaches with bacteria-based tumor therapy as an alternative treatment. In this context, live-attenuated bacteria, particularly Salmonella enterica, have demonstrated tumor selectivity, intrinsic oncolytic activity, and the ability to induce innate or specific antitumor immune responses. Moreover, Salmonella enterica also has strong potential as a delivery system of tumor-associated antigens, cytotoxic molecules, immunomodulatory molecules, pro-apoptotic proteins, and nucleic acids into eukaryotic cells, in a process known as bactofection and antitumor nanoparticles. In this review, we present the state of the art of current preclinical and clinical research on the use of Salmonella enterica as a potential therapeutic ally in the war against cancer. Full article
(This article belongs to the Special Issue Microbial-Based Cancer Therapies)
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