Delivery of viral-vectored vaccines by B cells represents a novel strategy to accelerate CD8+ T-cell recall responses

Zhang, Liang; Bridle, Byram W.; Chen, Lan; Pol, Jonathan; Spaner, David; Boudreau, Jeanette E.; Rosen, Allison B.; Bassett, Jennifer; Lichty, Brian D.; Bramson, Jonathan L.; Wan, Yonghong

doi:10.1182/blood-2012-06-438481

Cited by 36 publications

(33 citation statements)

References 46 publications

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“…Our in vitro analysis confirmed that infected B cells could transfer Ag to DCs without involving direct contact between the two cells although the exact form of the Ag remains to be determined. It was previously reported that B cells could carry viruses including VSV on their surface and transfer them to other cells (41,42), but our results argue that the Ag is likely in a different soluble form.…”

Section: Discussioncontrasting

confidence: 61%

Privileged Antigen Presentation in Splenic B Cell Follicles Maximizes T Cell Responses in Prime-Boost Vaccination

Bridle

Nguyen

Salem

et al. 2016

The Journal of Immunology

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Effector T cells (TEFF) are a barrier to booster vaccination because they can rapidly kill Ag-bearing APCs before memory T cells are engaged. We report in this study that i.v. delivery of rhabdoviral vectors leads to direct infection of follicular B cells in the spleen, where the earliest evidence of secondary T cell responses was observed. This allows booster immunizations to rapidly expand CD8+ central memory T cells (TCM) during the acute phase of the primary response that is dominated by TEFF. Interestingly, although the ablation of B cells before boosting with rhabdoviral vectors diminishes the expansion of memory T cells, B cells do not present Ags directly. Instead, depletion of CD11c+ dendritic cells abrogates secondary T cell expansion, suggesting that virus-infected follicular B cells may function as an Ag source for local DCs to subsequently capture and present the Ag. Because TCM are located within B cell follicles in the spleen whereas TEFF cannot traffic through follicular regions, Ag production and presentation by follicular APCs represent a unique mechanism to secure engagement of TCM during an ongoing effector response. Our data offer insights into novel strategies for rapid expansion of CD8+ T cells using prime-boost vaccines by targeting privileged sites for Ag presentation.

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Section: Discussioncontrasting

confidence: 61%

Privileged Antigen Presentation in Splenic B Cell Follicles Maximizes T Cell Responses in Prime-Boost Vaccination

Bridle

Nguyen

Salem

et al. 2016

The Journal of Immunology

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“…A unique study with oncolytic vaccines addressed this issue by delivering oncolytic vaccines with B cells. Here, the immunodominant gp33 peptide derived from lymphocytic choriomeningitis virus was expressed in three different viruses VSV, Ad, and VV to demonstrate that B cells loaded with the booster virus can elicit better antigen-specific secondary T cell responses, which were dependent on antigen presentation by dendritic cells (62). …”

Section: Heterologous Virus Prime-boost Strategiesmentioning

confidence: 99%

Sharpening the Edge for Precision Cancer Immunotherapy: Targeting Tumor Antigens through Oncolytic Vaccines

et al. 2017

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Cancer immunotherapy represents a promising, modern-age option for treatment of cancers. Among the many immunotherapies being developed, oncolytic viruses (OVs) are slowly moving to the forefront of potential clinical therapeutic agents, especially considering the fact that the first oncolytic virus was recently approved by the Food and Drug Administration for the treatment of melanoma. OVs were originally discovered for their ability to kill cancer cells, but they have emerged as unconventional cancer immunotherapeutics due to their ability to activate a long-term antitumor immune response. This immune response not only eliminates cancer cells but also offers potential for preventing cancer recurrence. A fundamental requirement for the generation of such a strong antitumor T cell response is the recognition of an immunogenic tumor antigen by the antitumor T cell. Several tumor antigens capable of activating these antitumor T cells have been identified and are now being expressed through genetically engineered OVs to potentiate antitumor immunity. With the emergence of novel technologies for identifying tumor antigens and immunogenic epitopes in a myriad of cancers, design of “oncolytic vaccines” expressing highly specific tumor antigens provides a great strategy for targeting tumors. Here, we highlight the various OVs engineered to target tumor antigens and discuss multiple studies and strategies used to develop oncolytic vaccine regimens. We also contend how, going forward, a combination of technologies for identifying novel immunogenic tumor antigens and rational design of oncolytic vaccines will pave the way for the next generation of clinically efficacious cancer immunotherapies.

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“…By means of an oncolytic rhabdovirus engineered to express TAA and using a prime-boost tumor vaccination approach, it was determined that TAA specific T-cell immune responses can be generated to protect mice from melanoma tumor challenge and lead to a significant diminution in lung metastases. Specific in vivo depletion of cytotoxic CD8 + T-cells during the boost vaccination abolished the therapeutic efficacy of the vaccine, highlighting their mediating role [79–81]. …”

Section: Mainmentioning

confidence: 99%

Combining surgery and immunotherapy: turning an immunosuppressive effect into a therapeutic opportunity

Bakos¹,

Lawson²,

Rouleau³

et al. 2018

j. immunotherapy cancer

142

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BackgroundCancer surgery is necessary and life-saving. However, the majority of patients develop postoperative recurrence and metastasis, which are the main causes of cancer-related deaths. The postoperative stress response encompasses a broad set of physiological changes that have evolved to safeguard the host following major tissue trauma. These stress responses, however, intersect with cellular mediators and signaling pathways that contribute to cancer proliferation.MainPrevious descriptive and emerging mechanistic studies suggest that the surgery-induced prometastatic effect is linked to impairment of both innate and adaptive immunity. Existing studies that combine surgery and immunotherapies have revealed that this combination strategy is not straightforward and patients have experienced both therapeutic benefit and drawbacks. This review will specifically assess the immunological pathways that are disrupted by oncologic surgical stress and provide suggestions for rationally combining cancer surgery with immunotherapies to improve immune and treatment outcomes.Short conclusionGiven the prevalence of surgery as frontline therapy for solid cancers, the emerging data on postoperative immunosuppression and the rapid development of immunotherapy for oncologic treatment, we believe that future targeted studies of perioperative immunotherapy are warranted.

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Delivery of viral-vectored vaccines by B cells represents a novel strategy to accelerate CD8+ T-cell recall responses

Abstract: • Using B cells to target antigens into the follicular regions represents a novel approach to accelerate CD81 T-cell recall responses.

Cited by 36 publications

References 46 publications

Privileged Antigen Presentation in Splenic B Cell Follicles Maximizes T Cell Responses in Prime-Boost Vaccination

Privileged Antigen Presentation in Splenic B Cell Follicles Maximizes T Cell Responses in Prime-Boost Vaccination

Sharpening the Edge for Precision Cancer Immunotherapy: Targeting Tumor Antigens through Oncolytic Vaccines

Combining surgery and immunotherapy: turning an immunosuppressive effect into a therapeutic opportunity

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