Tumor lysate-loaded Bacterial Ghosts as a tool for optimized production of therapeutic dendritic cell-based cancer vaccines

Dobrovolskiene, Neringa; Pašukonienė, Vita; Darinskas, Adas; Kraśko, Jan Aleksander; Žilionytė, Karolina; Mlynska, Agata; Gudlevičienė, Živilė; Mišeikytė-Kaubrienė, Edita; Schijns, Virgil E.J.C.; Lubitz, Werner; Kudela, Pavol; Strioga, Marius

doi:10.1016/j.vaccine.2018.06.016

Cited by 31 publications

(18 citation statements)

References 57 publications

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“…The first clinical trial on therapeutic cancer vaccine was carried out in 1998 on patients with melanoma [93]. Since the activation of the antigen-presenting ability of DCs is directly related with the induction of the CD8 + T cell response, researchers have focused on the modification of DCs in order to enhance the anti-tumor immune responses in vivo [94–96]. Many studies have demonstrated that most malignant tumors, including lung cancers, can produce a variety of factors that suppress anti-tumor immunity.…”

Section: Progress In the Clinical Application Of DC Function Restorationmentioning

confidence: 99%

Impaired dendritic cell functions in lung cancer: a review of recent advances and future perspectives

Wang

Huang

2019

Cancer Communications

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Lung cancer is the leading cause of cancer mortality worldwide. Dendritic cells (DCs) are the key factors providing protective immunity against lung tumors and clinical trials have proven that DC function is reduced in lung cancer patients. It is evident that the immunoregulatory network may play a key role in the failure of the immune response to terminate tumors. Lung tumors likely employ numerous strategies to suppress DC-based anti-tumor immunity. Here, we summarize the recent advances in our understanding on lung tumor-induced immunosuppression in DCs, which affects the initiation and development of T-cell responses. We also describe which existing measures to restore DC function may be useful for clinical treatment of lung tumors. Furthering our knowledge of how lung cancer cells alter DC function to generate a tumor-supportive environment will be essential in order to guide the design of new immunotherapy strategies for clinical use.

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Section: Progress In the Clinical Application Of DC Function Restorationmentioning

confidence: 99%

Impaired dendritic cell functions in lung cancer: a review of recent advances and future perspectives

Wang

Huang

2019

Cancer Communications

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“…Several types of TCL are able to induce DCs maturation at different degrees [8]; however most of them use LPS [33] or other adjuvants such as phytoextracts [34] and bacterial ghosts [35] in combination with the TCL. Our results show that PKHB1-induced cell death is able to promote DCs maturation and secretion of TNF α , even in the absence of other immune-stimulants.…”

Section: Resultsmentioning

confidence: 99%

PKHB1 Tumor Cell Lysate Induces Antitumor Immune System Stimulation and Tumor Regression in Syngeneic Mice with Tumoral T Lymphoblasts

Martínez‐Torres

Calvillo-Rodríguez

Uscanga‐Palomeque

et al. 2019

Journal of Oncology

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Acute lymphocytic leukemia (ALL) is the most common pediatric cancer. Currently, treatment options for patients with relapsed and refractory ALL mostly rely on immunotherapies. However, hematological cancers are commonly associated with a low immunogenicity and immune tolerance, which may contribute to leukemia relapse and the difficulties associated with the development of effective immunotherapies against this disease. We recently demonstrated that PKHB1, a TSP1-derived CD47 agonist peptide, induces immunogenic cell death (ICD) in T cell ALL (T-ALL). Cell death induced by PKHB1 on T-ALL cell lines and their homologous murine, L5178Y-R (T-murine tumor lymphoblast cell line), induced damage-associated molecular patterns (DAMPs) exposure and release. Additionally, a prophylactic vaccination with PKHB1-treated L5178Y-R cells prevented tumor establishment in vivo in all the cases. Due to the immunogenic potential of PKHB1-treated cells, in this study we assessed their ability to induce antitumor immune responses ex vivo and in vivo in an established tumor. We first confirmed the selectivity of cell death induced by PKBH1 in tumor L5178Y-R cells and observed that calreticulin exposure increased when cell death increased. Then, we found that the tumor cell lysate (TCL) obtained from PKHB1-treated L5178YR tumor cells (PKHB1-TCL) was able to induce, ex vivo, dendritic cells maturation, cytokine production, and T cell antitumor responses. Finally, our results show that in vivo, PKHB1-TCL treatment induces tumor regression in syngeneic mice transplanted with L5178Y-R cells, increasing their overall survival and protecting them from further tumor establishment after tumor rechallenge. Altogether our results highlight the immunogenicity of the cell death induced by PKHB1 activation of CD47 as a potential therapeutic tool to overcome the low immunogenicity and immune tolerance in T-ALL.

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“…Another new delivery approach that has been studied utilizes bacterial ghosts [ 168 , 169 , 170 ], where a native bacterial outer membrane (with or without LPS [ 170 ]) is utilized to encapsulate the desired antigen. This was reported to be effective in inducing dendritic cell maturation in comparison to LPS-based protocols [ 168 ], but may carry the risk of a too-low specific antibody titer. A third approach has been to use nanocarriers to encapsulate an antigenic payload [ 91 , 171 , 172 , 173 ].…”

Section: Alternative Immunization Approaches From Other Research Fmentioning

confidence: 99%

Innovative Immunization Strategies for Antivenom Development

Bermúdez-Méndez

Fuglsang-Madsen

Føns

et al. 2018

Toxins

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Snakes, scorpions, and spiders are venomous animals that pose a threat to human health, and severe envenomings from the bites or stings of these animals must be treated with antivenom. Current antivenoms are based on plasma-derived immunoglobulins or immunoglobulin fragments from hyper-immunized animals. Although these medicines have been life-saving for more than 120 years, opportunities to improve envenoming therapy exist. In the later decades, new biotechnological tools have been applied with the aim of improving the efficacy, safety, and affordability of antivenoms. Within the avenues explored, novel immunization strategies using synthetic peptide epitopes, recombinant toxins (or toxoids), or DNA strings as immunogens have demonstrated potential for generating antivenoms with high therapeutic antibody titers and broad neutralizing capacity. Furthermore, these approaches circumvent the need for venom in the production process of antivenoms, thereby limiting some of the complications associated with animal captivity and venom collection. Finally, an important benefit of innovative immunization approaches is that they are often compatible with existing antivenom manufacturing setups. In this review, we compile all reported studies examining venom-independent innovative immunization strategies for antivenom development. In addition, a brief description of toxin families of medical relevance found in snake, scorpion, and spider venoms is presented, as well as how biochemical, bioinformatic, and omics tools could aid the development of next-generation antivenoms.

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Tumor lysate-loaded Bacterial Ghosts as a tool for optimized production of therapeutic dendritic cell-based cancer vaccines

Cited by 31 publications

References 57 publications

Impaired dendritic cell functions in lung cancer: a review of recent advances and future perspectives

Impaired dendritic cell functions in lung cancer: a review of recent advances and future perspectives

PKHB1 Tumor Cell Lysate Induces Antitumor Immune System Stimulation and Tumor Regression in Syngeneic Mice with Tumoral T Lymphoblasts

Innovative Immunization Strategies for Antivenom Development

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