A vector-encoded bispecific killer engager to harness virus-activated NK cells as anti-tumor effectors

Floerchinger, Alessia; Klein, Jessica E.; Finkbeiner, Maximiliane S. C.; Schäfer, Theresa E.; Fuchs, Gwendolin; Doerner, Johannes; Zirngibl, Hubert; Ackermann, Maximilian; Kvasnicka, H. M.; Chester, Kerry; Jäger, Dirk; Ball, Claudia R.; Ungerechts, Guy; Engeland, Christine E.

doi:10.1038/s41419-023-05624-3

Cited by 6 publications

(2 citation statements)

References 65 publications

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“…These may include opportunities to prevent CD16a cleavage with matrix metalloproteinase inhibitors, or cellular therapies with non-cleavable CD16a + molecules ( 45 – 47 ). Immunologic modifiers, such as immune checkpoint inhibitors that rescue leukocytes from inhibition and anergy, or bi- and tri-specific engagers that force interactions between key immune populations could change the immune contexture to make patients’ tumors more amenable for immune recognition ( 48 – 50 ).…”

Section: Discussionmentioning

confidence: 99%

Improved overall survival in patients with high-grade serous ovarian cancer is associated with CD16a+ immunologic neighborhoods containing NK cells, T cells and macrophages

Nersesian,

Arseneau,

Mejia

et al. 2024

Front. Immunol.

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BackgroundFor patients with high grade serous carcinoma of the ovary (HGSC), survival rates have remained static for the last half century. Despite the presence of tumor mutations and infiltration of immune cells, existing immunotherapies have achieved little success against HGSC. These observations highlight a gap in the understanding of how the immune system functions and interacts within HGSC tumors.MethodsWe analyzed duplicate core samples from 939 patients with HGSC to understand patterns of immune cell infiltration, localization, and associations with clinical features. We used high-parameter immunohistochemical/Opal multiplex, digital pathology, computational biology, and multivariate analysis to identify immune cell subsets and their associations with HGSC tumors.ResultsWe defined six patterns of cellular infiltration by spatially restricted unsupervised clustering of cell subsets. Each pattern was represented to some extent in most patient samples, but their specific distributions differed. Overall (OS) and progression-free survival (PFS) corresponded with higher infiltration of CD16a+ cells, and their co-localization with macrophages, T cells, NK cells, in one of six cellular neighborhoods that we defined with our spatial assessment.ConclusionsImmune cell neighborhoods containing CD16a+ cells are associated with improved OS and PFS for patients with HGSC. Patterns of immunologic neighborhoods differentiate patient outcomes, and could inform future, more precise approaches to treatment.

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Section: Discussionmentioning

confidence: 99%

Improved overall survival in patients with high-grade serous ovarian cancer is associated with CD16a+ immunologic neighborhoods containing NK cells, T cells and macrophages

Nersesian,

Arseneau,

Mejia

et al. 2024

Front. Immunol.

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show abstract

“…[398][399][400][401] To improve the cytotoxic activity against tumor cells directed by MeV-activated NK cells, oncolytic MeV vaccines encoding both CD16A on NK cells and carcinoembryonic antigen (CEA) as a model tumor antigen was developed, termed bispecific killer engagers (MV-BiKE). 402 MV-BiKE mediated the secretion of functional BiKE from infected tumor cells. In colorectal or pancreatic cancer cells, MV-BiKE specified the anti-tumor cytotoxicity by NK cells and mediated expression of effector cytokines and degranulation.…”

Section: Application Of Viral Vectors As Therapeutic Vaccines Against...mentioning

confidence: 99%

Viral vectored vaccines: design, development, preventive and therapeutic applications in human diseases

Wang

Liang

Wang

et al. 2023

Sig Transduct Target Ther

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Human diseases, particularly infectious diseases and cancers, pose unprecedented challenges to public health security and the global economy. The development and distribution of novel prophylactic and therapeutic vaccines are the prioritized countermeasures of human disease. Among all vaccine platforms, viral vector vaccines offer distinguished advantages and represent prominent choices for pathogens that have hampered control efforts based on conventional vaccine approaches. Currently, viral vector vaccines remain one of the best strategies for induction of robust humoral and cellular immunity against human diseases. Numerous viruses of different families and origins, including vesicular stomatitis virus, rabies virus, parainfluenza virus, measles virus, Newcastle disease virus, influenza virus, adenovirus and poxvirus, are deemed to be prominent viral vectors that differ in structural characteristics, design strategy, antigen presentation capability, immunogenicity and protective efficacy. This review summarized the overall profile of the design strategies, progress in advance and steps taken to address barriers to the deployment of these viral vector vaccines, simultaneously highlighting their potential for mucosal delivery, therapeutic application in cancer as well as other key aspects concerning the rational application of these viral vector vaccines. Appropriate and accurate technological advances in viral vector vaccines would consolidate their position as a leading approach to accelerate breakthroughs in novel vaccines and facilitate a rapid response to public health emergencies.

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Tutorial: design, production and testing of oncolytic viruses for cancer immunotherapy

Gujar,

Pol,

Kumar

et al. 2024

Nat Protoc

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A vector-encoded bispecific killer engager to harness virus-activated NK cells as anti-tumor effectors

Cited by 6 publications

References 65 publications

Improved overall survival in patients with high-grade serous ovarian cancer is associated with CD16a+ immunologic neighborhoods containing NK cells, T cells and macrophages

Improved overall survival in patients with high-grade serous ovarian cancer is associated with CD16a+ immunologic neighborhoods containing NK cells, T cells and macrophages

Viral vectored vaccines: design, development, preventive and therapeutic applications in human diseases

Tutorial: design, production and testing of oncolytic viruses for cancer immunotherapy

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