Immunomodulatory potential of in vivo natural killer T (NKT) activation by NKTT320 in Mauritian-origin cynomolgus macaques

Bond, Nell G.; Fahlberg, Marissa; Shi, Yu; Rout, Namita; Tran, Dollnovan; Fitzpatrick-Schmidt, Taylor; Sprehe, Lesli M.; Scheef, Elizabeth A.; Mudd, Joseph C.; Schaub, Robert G.; Kaur, Amitinder

doi:10.1016/j.isci.2022.103889

Cited by 2 publications

(1 citation statement)

References 91 publications

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“…iNKT cell activation was shown to enhance antigen-specific CD4+ and CD8+ T cell responses to a HIV DNA vaccine in mice, with the effect being observed during DNA priming [ 223 ]. We demonstrated the effects of iNKT activation in an NHP model of Mauritian-origin cynomolgus macaques and showed the downstream activation effects on CD4+ T-lymphocytes, monocytes, dendritic cells and B cells [ 224 ]. Harnessing the immunotherapeutic potential of iNKT activation may be another useful tool for potentiating HIV vaccine efficacy, which can be tested in the NHP model.…”

Section: Vaccine Induced Correlates Of Hiv In Humans and Nhpmentioning

confidence: 99%

Exploring HIV Vaccine Progress in the Pre-Clinical and Clinical Setting: From History to Future Prospects

Kaur,

Vaccari

2024

Viruses

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The human immunodeficiency virus (HIV) continues to pose a significant global health challenge, with millions of people affected and new cases emerging each year. While various treatment and prevention methods exist, including antiretroviral therapy and non-vaccine approaches, developing an effective vaccine remains the most crucial and cost-effective solution to combating the HIV epidemic. Despite significant advancements in HIV research, the HIV vaccine field has faced numerous challenges, and only one clinical trial has demonstrated a modest level of efficacy. This review delves into the history of HIV vaccines and the current efforts in HIV prevention, emphasizing pre-clinical vaccine development using the non-human primate model (NHP) of HIV infection. NHP models offer valuable insights into potential preventive strategies for combating HIV, and they play a vital role in informing and guiding the development of novel vaccine candidates before they can proceed to human clinical trials.

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Section: Vaccine Induced Correlates Of Hiv In Humans and Nhpmentioning

confidence: 99%

Exploring HIV Vaccine Progress in the Pre-Clinical and Clinical Setting: From History to Future Prospects

Kaur,

Vaccari

2024

Viruses

Self Cite

View full text Add to dashboard Cite

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T Cell Receptor-Engaging Monoclonal Antibodies Mobilize the Anti-Tumor Functions of Invariant Natural Killer T Cells

Das

2024

Crit Rev Oncog

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Invariant natural killer T cells (iNKTs) are innate-type T lymphocytes that directly kill tumor cells or tumor-growth promoting immunosuppressive cells such astumor-associated macrophages. Additionally, iNKTs robustly transactivate the antitumor functions of T, B, natural killer, and dendritic cells as well as reinvigorate exhausted immune cells in the tumor microenvironment. As such, iNKTs make excellent candidates for inclusion in anti-cancer cellular therapies. However, to capitalize on the potential benefits of iNKT cell-based approaches, it is imperative that we develop new and clinically viable strategies to enhance their antitumor function. To that end, two novel monoclonal antibodies (mAbs) that selectively bind to the human (NKTT320) or murine (NKT14m) invariant T cell receptor have been recently developed and characterized. Studies using purified human iNKTs (in vitro) and a model of non-human primate (in vivo) reveal that NKTT320 promotes swift, vigorous and sustained iNKT cell activation that is accompanied by robust production of inflammatory mediators and bystander immune cell activation. Furthermore, NKTT320 augments expression of cytotoxic markers and human iNKT cell degranulation. Similarly, NKT14m prompts dramatic murine iNKT cell activation and functional response both in vitro and in vivo. However, antitumor efficacy of a single dose of NKT14m injection in tumor-bearing mice is limited and tumor-model dependent. In contrast, combination treatment of NKT14m with either low dose interleukin (IL)-12 or the chemotherapeutic agent, cyclophosphamide results in a superior antitumor response in vivo. This is evident by activation of both iNKTs and other immune cells, prolonged survival of the tumor-challenged mice, and long-lasting immunity. Collectively, these recent studies justify further development of anti-iTCR mAbs that can be used alone or in conjunction with immunomodulatory agents to enhance iNKT cell antitumor immunity against various cancers.

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Immunomodulatory potential of in vivo natural killer T (NKT) activation by NKTT320 in Mauritian-origin cynomolgus macaques

Cited by 2 publications

References 91 publications

Exploring HIV Vaccine Progress in the Pre-Clinical and Clinical Setting: From History to Future Prospects

Exploring HIV Vaccine Progress in the Pre-Clinical and Clinical Setting: From History to Future Prospects

T Cell Receptor-Engaging Monoclonal Antibodies Mobilize the Anti-Tumor Functions of Invariant Natural Killer T Cells

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