Bacterial-Based Cancer Therapy (BBCT): Recent Advances, Current Challenges, and Future Prospects for Cancer Immunotherapy

Currently approximately 10 million people die each year due to cancer, and cancer is the cause of every sixth death worldwide. Tremendous efforts and progress have been made towards finding a cure for cancer. However, numerous challenges have been faced due to adverse effects of chemotherapy, radiotherapy, and alternative cancer therapies, including toxicity to non-cancerous cells, the inability of drugs to reach deep tumor tissue, and the persistent problem of increasing drug resistance in tumor cells. These challenges have increased the demand for the development of alternative approaches with greater selectivity and effectiveness against tumor cells. Cancer immunotherapy has made significant advancements towards eliminating cancer. Our understanding of cancer-directed immune responses and the mechanisms through which immune cells invade tumors have extensively helped us in the development of new therapies. Among immunotherapies, the application of bacteria and bacterial-based products has promising potential to be used as treatments that combat cancer. Bacterial targeting of tumors has been developed as a unique therapeutic option that meets the ongoing challenges of cancer treatment. In comparison with other cancer therapeutics, bacterial-based therapies have capabilities for suppressing cancer. Bacteria are known to accumulate and proliferate in the tumor microenvironment and initiate antitumor immune responses. We are currently well-informed regarding various methods by which bacteria can be manipulated by simple genetic engineering or synthetic bioengineering to induce the production of anti-cancer drugs. Further, bacterial-based cancer therapy (BBCT) can be either used as a monotherapy or in combination with other anticancer therapies for better clinical outcomes. Here, we review recent advances, current challenges, and prospects of bacteria and bacterial products in the development of BBCTs.

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Recent Advances in Gelatin-Based Nanomedicine for Targeted Delivery of Anti-Cancer Drugs

Current Pharmaceutical Design ◽

10.2174/1381612827666211102100118 ◽

2021 ◽

Vol 27 ◽

Author(s):

Faisal Raza ◽

Liu Siyu ◽

Hajra Zafar ◽

Zul Kamal ◽

Bo Zheng ◽

...

Keyword(s):

Cancer Therapy ◽

Targeted Delivery ◽

Cancer Therapeutics ◽

Natural Polymers ◽

Gelatin Nanoparticles ◽

Good Surface ◽

Recent Advances ◽

Wide Range ◽

Anti Cancer ◽

Cancer Nanomedicine

: Nanoparticles based on natural polymers are utilized for the development of a wide range of drug delivery systems (DDS) in the current era. Gelatin-based nanoparticles, for example, are a remarkable cancer therapy with high efficacy and specificity. This paper reviews the recent advancements in gelatin-based nanomedicine for use in cancer therapeutics. Due to the characteristics features of gelatin, such as biocompatibility, biodegradability, stability, and good surface properties, these nanoparticles provide high therapeutic potency in cancer nanomedicine. The surface of gelatin can be modified in a number of ways using various ligands to explore the platform for the development of a more novel DDS. Various methods are available for the preparation of gelatin nanomedicine discussed in this review. In addition, various cross-linkers to stabilized nanocarriers and stimuli base gelatin nanoparticles are reviewed. Furthermore, recent advances and research in gelatin-based nanomedicine are discussed. Also, some drawbacks and challenges are evaluated. In general, this paper paves the pathway to identify the details about the gelatin-based DDS for cancer therapy.

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Immunomodulating nano-adaptors potentiate antibody-based cancer immunotherapy

Nature Communications ◽

10.1038/s41467-021-21497-6 ◽

2021 ◽

Vol 12 (1) ◽

Cited By ~ 1

Author(s):

Cheng-Tao Jiang ◽

Kai-Ge Chen ◽

An Liu ◽

Hua Huang ◽

Ya-Nan Fan ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Immune Responses ◽

Cancer Immunotherapy ◽

Tumor Cells ◽

Noncovalent Interactions ◽

Killer Cell ◽

Antibody Immobilization ◽

Effector Cells ◽

Nanoparticle Surface

AbstractModulating effector immune cells via monoclonal antibodies (mAbs) and facilitating the co-engagement of T cells and tumor cells via chimeric antigen receptor- T cells or bispecific T cell-engaging antibodies are two typical cancer immunotherapy approaches. We speculated that immobilizing two types of mAbs against effector cells and tumor cells on a single nanoparticle could integrate the functions of these two approaches, as the engineered formulation (immunomodulating nano-adaptor, imNA) could potentially associate with both cells and bridge them together like an ‘adaptor’ while maintaining the immunomodulatory properties of the parental mAbs. However, existing mAbs-immobilization strategies mainly rely on a chemical reaction, a process that is rough and difficult to control. Here, we build up a versatile antibody immobilization platform by conjugating anti-IgG (Fc specific) antibody (αFc) onto the nanoparticle surface (αFc-NP), and confirm that αFc-NP could conveniently and efficiently immobilize two types of mAbs through Fc-specific noncovalent interactions to form imNAs. Finally, we validate the superiority of imNAs over the mixture of parental mAbs in T cell-, natural killer cell- and macrophage-mediated antitumor immune responses in multiple murine tumor models.

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The Origins and Generation of Cancer-Associated Mesenchymal Stromal Cells: An Innovative Therapeutic Target for Solid Tumors

Frontiers in Oncology ◽

10.3389/fonc.2021.723707 ◽

2021 ◽

Vol 11 ◽

Author(s):

Wei Li ◽

Jin Yang ◽

Ping Zheng ◽

Haining Li ◽

Shaolin Zhao

Keyword(s):

Cancer Therapy ◽

Tumor Cells ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Chemotherapy Resistance ◽

Tissue Type ◽

Cell Contact ◽

Local Resident ◽

Anti Cancer ◽

Direct Cell

Cancer-associated mesenchymal stromal cells (CA-MSCs) have been isolated from various types of tumors and are characterized by their vigorous pro-tumorigenic functions. However, very little is known about the origins and generating process of CA-MSCs, which may facilitate the identification of biomarkers for diagnosis or innovative targets for anti-cancer therapy to restrain the tumor growth, spread and chemotherapy resistance. Current evidences have indicated that both distally recruited and local resident MSCs are the primary origins of CA-MSCs. In a tissue type-dependent mode, tumor cells together with the TME components prompt the malignant transition of tumor “naïve” MSCs into CA-MSCs in a direct cell-to-cell contact, paracrine or exosome-mediated manner. In this review, we discuss the transition of phenotypes and functions of naïve MSCs into CA-MSCs influenced by tumor cells or non-tumor cells in the TME. The key areas remaining poorly understood are also highlighted and concluded herein.

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Immune Responses to COVID-19 mRNA Vaccines in Patients with Solid Tumors on Active, Immunosuppressive Cancer Therapy

10.1101/2021.05.13.21257129 ◽

2021 ◽

Author(s):

Rachna T Shroff ◽

Pavani Chalasani ◽

Ran Wei ◽

Daniel Pennington ◽

Grace Quirk ◽

...

Keyword(s):

Cancer Therapy ◽

Immune Responses ◽

Cancer Patients ◽

Neutralizing Antibodies ◽

Fold Increase ◽

Control Cohort ◽

Tumor Patients ◽

Specific Memory ◽

Anti Cancer ◽

B Cell Subsets

Vaccines against SARS-CoV-2 have shown high efficacy, but immunocompromised participants were excluded from controlled clinical trials. We evaluated immune responses to the Pfizer/BioNTech mRNA vaccine in solid tumor patients (n=52) on active cytotoxic anti-cancer therapy. These responses were compared to a control cohort that also received the Pfizer/BioNTech vaccine (n=50). Using live SARS-CoV-2 assays, neutralizing antibodies were detected in 67% and 80% of cancer patients after the first and second immunizations, respectively, with a 3-fold increase in median titers after the booster. Similar trends were observed in serum antibodies against the receptor-binding domain (RBD) and S2 regions of Spike protein, and in IFN𝛾+ Spike-specific T cells. The magnitude of each of these responses was diminished relative to the control cohort. We therefore quantified RBD- and Spike S1-specific memory B cell subsets as predictors of anamnestic responses to viral exposures or additional immunizations. After the second vaccination, Spike-specific plasma cell-biased memory B cells were observed in most cancer patients at levels similar to those of the control cohort after the first immunization. These data suggest that a third immunization might elevate antibody responses in cancer patients to levels seen in healthy individuals after the second dose. Trials should be conducted to test these predictions.

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Breast Cancer Therapeutics Based on Fusarochromanone and EGFR Inhibitors

10.21203/rs.3.rs-289662/v1 ◽

2021 ◽

Author(s):

Natalie Carroll ◽

Alena Smith ◽

Brian A. Salvatore ◽

Elahe Mahdavian

Keyword(s):

Breast Cancer ◽

Mode Of Action ◽

Cancer Therapeutics ◽

Egfr Inhibitors ◽

Cancer Therapies ◽

Racemic Form ◽

Combination Treatments ◽

Anti Cancer ◽

Cancer Agent ◽

Cancer Activity

Abstract Background: Fusarochromanone (FC101) is a small molecule with potent anti-cancer activity. It was originally derived from the fungal plant pathogen, Fusarium equiseti, and it has also been synthesized in non-racemic form in our lab. Numerous studies reveal the promising biological activity of FC101, including potent anti-angiogenic and anti-cancer activity. While FC101 is potent as a single drug treatment across many cancer cell lines, current cancer therapies often incorporate a combination of drugs in order to increase efficacy and decrease the development of drug resistance. In this study, we leverage drug combinations and cellular phenotypic screens to address important questions about FC101’s mode of action and its potential synergies as an anti-cancer therapeutic agent in triple negative breast cancer (TNBC).Method: We hypothesized that FC101’s activity against TNBC is similar to the known mTOR inhibitor, everolimus, because FC101 reduces the phosphorylation of two key mTOR substrates, S6K and S6. Since everolimus synergistically enhances the anti-cancer activities of known EGFR inhibitors (erlotinib or lapatinib) in TNBC, we performed analogous studies with FC101. Phenotypic cellular assays helped assess whether FC101 (in both single and combination treatments) acts similarly to everolimus.Results: FC101 outperformed all other single treatments in both cell proliferation and viability assays. Unlike everolimus, however, FC101 brought about a sustained decrease in cell viability in drug washout studies. None of the other drugs were able to maintain comparable effects upon removal of the treatment agents. Although we observed slightly additive effects when the TNBC cells were treated with FC101 and either EGFR inhibitor, those effects were not truly synergistic in the manner displayed with everolimus. Conclusion: Our results rule out direct inhibition of mTOR by FC101 and suggest that FC101 acts through a different mechanism than everolimus. This lays the foundation for the refinement of our hypothesis in order to better understand FC101’s mode of action as a novel anti-cancer agent.

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The Complex Cancer Care Coverage Environment — What is the Role of Legislation?

The Journal of Law Medicine & Ethics ◽

10.1177/1073110520958879 ◽

2020 ◽

Vol 48 (3) ◽

pp. 538-551 ◽

Cited By ~ 1

Author(s):

Christine Leopold ◽

Rebecca L. Haffajee ◽

Christine Y. Lu ◽

Anita K. Wagner

Keyword(s):

Cancer Care ◽

Insurance Coverage ◽

Cancer Therapeutics ◽

Health Insurance Coverage ◽

Cancer Therapies ◽

Cancer Treatments ◽

Difficult Situation ◽

Cell Therapies ◽

State Laws ◽

Anti Cancer

Over the past decades, anti-cancer treatments have evolved rapidly from cytotoxic chemotherapies to targeted therapies including oral targeted medications and injectable immunooncology and cell therapies. New anti-cancer medications come to markets at increasingly high prices, and health insurance coverage is crucial for patient access to these therapies. State laws are intended to facilitate insurance coverage of anti-cancer therapies.Using Massachusetts as a case study, we identified five current cancer coverage state laws and interviewed experts on their perceptions of the relevance of the laws and how well they meet the current needs of cancer care given rapid changes in therapies. Interviewees emphasized that cancer therapies, as compared to many other therapeutic areas, are unique because insurance legislation targets their coverage. They identified the oral chemotherapy parity law as contributing to increasing treatment costs in commercial insurance. For commercial insurers, coverage mandates combined with the realities of new cancer medications — including high prices and often limited evidence of efficacy at approval — compound a difficult situation. Respondents recommended policy approaches to address this challenging coverage environment, including the implementation of closed formularies, the use of cost-effectiveness studies to guide coverage decisions, and the application of value-based pricing concepts. Given the evolution of cancer therapeutics, it may be time to evaluate the benefits and challenges of cancer coverage mandates.

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Epigenetic Research in Stem Cell Bioengineering—Anti-Cancer Therapy, Regenerative and Reconstructive Medicine in Human Clinical Trials

Cancers ◽

10.3390/cancers12041016 ◽

2020 ◽

Vol 12 (4) ◽

pp. 1016 ◽

Cited By ~ 1

Author(s):

Claudia Dompe ◽

Krzysztof Janowicz ◽

Greg Hutchings ◽

Lisa Moncrieff ◽

Maurycy Jankowski ◽

...

Keyword(s):

Gene Expression ◽

Clinical Trials ◽

Stem Cell ◽

Cancer Therapy ◽

Regulation Of Gene Expression ◽

Epigenetic Modifications ◽

Transcriptional Level ◽

Cancer Therapies ◽

Stem Cell Engineering ◽

Anti Cancer

The epigenome denotes all the information related to gene expression that is not contained in the DNA sequence but rather results from chemical changes to histones and DNA. Epigenetic modifications act in a cooperative way towards the regulation of gene expression, working at the transcriptional or post-transcriptional level, and play a key role in the determination of phenotypic variations in cells containing the same genotype. Epigenetic modifications are important considerations in relation to anti-cancer therapy and regenerative/reconstructive medicine. Moreover, a range of clinical trials have been performed, exploiting the potential of epigenetics in stem cell engineering towards application in disease treatments and diagnostics. Epigenetic studies will most likely be the basis of future cancer therapies, as epigenetic modifications play major roles in tumour formation, malignancy and metastasis. In fact, a large number of currently designed or tested clinical approaches, based on compounds regulating epigenetic pathways in various types of tumours, employ these mechanisms in stem cell bioengineering.

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Microbes as Medicines: Harnessing the Power of Bacteria in Advancing Cancer Treatment

International Journal of Molecular Sciences ◽

10.3390/ijms21207575 ◽

2020 ◽

Vol 21 (20) ◽

pp. 7575 ◽

Cited By ~ 1

Author(s):

Shruti S. Sawant ◽

Suyash M. Patil ◽

Vivek Gupta ◽

Nitesh K. Kunda

Keyword(s):

Cancer Therapy ◽

Cancer Treatment ◽

Treatment Options ◽

Current Treatment ◽

Genetically Engineered ◽

Cancer Therapies ◽

Anti Cancer ◽

Tumor Environment ◽

Systemic Side Effects ◽

Hypoxic Tumor

Conventional anti-cancer therapy involves the use of chemical chemotherapeutics and radiation and are often non-specific in action. The development of drug resistance and the inability of the drug to penetrate the tumor cells has been a major pitfall in current treatment. This has led to the investigation of alternative anti-tumor therapeutics possessing greater specificity and efficacy. There is a significant interest in exploring the use of microbes as potential anti-cancer medicines. The inherent tropism of the bacteria for hypoxic tumor environment and its ability to be genetically engineered as a vector for gene and drug therapy has led to the development of bacteria as a potential weapon against cancer. In this review, we will introduce bacterial anti-cancer therapy with an emphasis on the various mechanisms involved in tumor targeting and tumor suppression. The bacteriotherapy approaches in conjunction with the conventional cancer therapy can be effective in designing novel cancer therapies. We focus on the current progress achieved in bacterial cancer therapies that show potential in advancing existing cancer treatment options and help attain positive clinical outcomes with minimal systemic side-effects.

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Targeting ERK-Hippo Interplay in Cancer Therapy

International Journal of Molecular Sciences ◽

10.3390/ijms21093236 ◽

2020 ◽

Vol 21 (9) ◽

pp. 3236 ◽

Cited By ~ 2

Author(s):

Karel Vališ ◽

Petr Novák

Keyword(s):

Cancer Therapy ◽

Signaling Pathways ◽

Signaling Pathway ◽

Cross Talk ◽

Mapk Signaling ◽

Mapk Signaling Pathway ◽

Mitogen Activated Protein Kinase ◽

Cancer Therapies ◽

Anti Cancer ◽

Targeted Inhibition

Extracellular signal-regulated kinase (ERK) is a part of the mitogen-activated protein kinase (MAPK) signaling pathway which allows the transduction of various cellular signals to final effectors and regulation of elementary cellular processes. Deregulation of the MAPK signaling occurs under many pathological conditions including neurodegenerative disorders, metabolic syndromes and cancers. Targeted inhibition of individual kinases of the MAPK signaling pathway using synthetic compounds represents a promising way to effective anti-cancer therapy. Cross-talk of the MAPK signaling pathway with other proteins and signaling pathways have a crucial impact on clinical outcomes of targeted therapies and plays important role during development of drug resistance in cancers. We discuss cross-talk of the MAPK/ERK signaling pathway with other signaling pathways, in particular interplay with the Hippo/MST pathway. We demonstrate the mechanism of cell death induction shared between MAPK/ERK and Hippo/MST signaling pathways and discuss the potential of combination targeting of these pathways in the development of more effective anti-cancer therapies.

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Application of Nanocomposites in Cancer Immunotherapy

Nano LIFE ◽

10.1142/s1793984417500088 ◽

2017 ◽

Vol 07 (03n04) ◽

pp. 1750008

Author(s):

Wenhan Liu ◽

Zejun Wang ◽

Yao Luo ◽

Nan Chen

Keyword(s):

Immune System ◽

Cancer Therapy ◽

Cancer Treatment ◽

Cancer Immunotherapy ◽

Cancer Patients ◽

Tumor Cells ◽

Tumor Immunity ◽

Critical Role ◽

Clinical Advances ◽

Review Current

Despite the clinical advances in oncology, cancer is still the major cause of death worldwide. Recent research demonstrates that the immune system plays a critical role in preventing tumor occurrence and development. The focus on cancer treatment has been shifted from directly targeting the tumor cells to motivating the immune system to achieve this goal. However, the activity of immune system is often suppressed in cancer patients. To boost the anti-tumor immunity against cancers, various nanocomposites have been developed to enhance the efficacy of immunostimulatory agents. Here, we review current advances in nanomaterial-mediated immunotherapy for the treatment of cancer, with an emphasis on applications of nanocomposites as immunoadjuvants in cancer therapy.

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