Revolutionizing Human papillomavirus (HPV)‐related cancer therapies: Unveiling the promise of Proteolysis Targeting Chimeras (PROTACs) and Proteolysis Targeting Antibodies (PROTABs) in cancer nano‐vaccines

Mukerjee, Nobendu; Maitra, Swastika; Gorai, Sukhamoy; Ghosh, Arabinda; Alexiou, Athanasiosis; Thorat, Nanasaheb D.

doi:10.1002/jmv.29135

Cited by 8 publications

(6 citation statements)

References 21 publications

(67 reference statements)

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“…PROTACs in Vaccine Development: PROTACs are primarily used in the targeted degradation of specific proteins within cells, a concept that is not commonly associated with vaccine development. 136 Their utilization in vaccines would require innovative approaches and may not be a conventional solution to common vaccine challenges. Customizing vaccine designs for optimal antigen presentation by expert APCs and locating combination partners using complementary mechanisms of action further add complexity to the task.…”

Section: Mechanism Of Action Of Cancer Vaccinementioning

confidence: 99%

“…Ensuring the safety, scalability, and efficacy of exosome-based vaccines in humans is an ongoing concern PROTACs in Vaccine Development: PROTACs are primarily used in the targeted degradation of specific proteins within cells, a concept that is not commonly associated with vaccine development . Their utilization in vaccines would require innovative approaches and may not be a conventional solution to common vaccine challenges. Common Limitations and Challenges: Both exosome-based vaccines and PROTACs must ensure safety and minimal immunogenicity when administered to patients.…”

Section: Types Of Cancer Vaccines: a Comprehensive Overviewmentioning

confidence: 99%

Section: Types Of Cancer Vaccines: a Comprehensive Overviewmentioning

confidence: 99%

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Revolutionizing Cancer Treatment: Unleashing the Power of Viral Vaccines, Monoclonal Antibodies, and Proteolysis-Targeting Chimeras in the New Era of Immunotherapy

Mohite,

Yadav,

Pandhare

et al. 2024

ACS Omega

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In the realm of cancer immunotherapy, a profound evolution has ushered in sophisticated strategies that encompass both traditional cancer vaccines and emerging viral vaccines. This comprehensive Review offers an in-depth exploration of the methodologies, clinical applications, success stories, and future prospects of these approaches. Traditional cancer vaccines have undergone significant advancements utilizing diverse modalities such as proteins, peptides, and dendritic cells. More recent innovations have focused on the physiological mechanisms enabling the human body to recognize and combat precancerous and malignant cells, introducing specific markers like peptide-based anticancer vaccines targeting tumor-associated antigens. Moreover, cancer viral vaccines, leveraging engineered viruses to stimulate immune responses against specific antigens, exhibit substantial promise in inducing robust and enduring immunity. Integration with complementary therapeutic methods, including monoclonal antibodies, adjuvants, and radiation therapy, has not only improved survival rates but also deepened our understanding of viral virulence. Recent strides in vaccine design, encompassing oncolytic viruses, virus-like particles, and viral vectors, mark the frontier of innovation. While these advances hold immense potential, critical challenges must be addressed, such as strategies for immune evasion, potential off-target effects, and the optimization of viral genomes. In the landscape of immunotherapy, noteworthy innovations take the spotlight from the use of immunomodulatory agents for the enhancement of innate and adaptive immune collaboration. The emergence of proteolysis-targeting chimeras (PROTACs) as precision tools for cancer therapy is particularly exciting. With a focus on various cancers, from melanoma to formidable solid tumors, this Review critically assesses types of cancer vaccines, mechanisms, barriers in vaccine therapy, vaccine efficacy, safety profiles, and immune-related adverse events, providing a nuanced perspective on the underlying mechanisms involving cytotoxic T cells, natural killer cells, and dendritic cells. The Review also underscores the transformative potential of cutting-edge technologies such as clinical studies, molecular sequencing, and artificial intelligence in advancing the field of cancer vaccines. These tools not only expedite progress but also emphasize the multidimensional and rapidly evolving nature of this research, affirming its profound significance in the broader context of cancer therapy. ■ UNRAVELING THE COMPLEXITY OF CANCER TREATMENT: A COMPREHENSIVE OVERVIEW OF MODERN INNOVATIONS AND EMERGING TECHNOLOGIESCancer, a word synonymous with uncertainty, suffering, and complexity, has emerged as a multifaceted challenge that transcends biological understanding and societal boundaries. As the leading cause of mortality worldwide, it prompts an immediate yet intricate response from the medical and scientific communities. The panorama of cancer is vast, encompassing various types and stages, ...

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Section: Mechanism Of Action Of Cancer Vaccinementioning

confidence: 99%

Section: Types Of Cancer Vaccines: a Comprehensive Overviewmentioning

confidence: 99%

Section: Types Of Cancer Vaccines: a Comprehensive Overviewmentioning

confidence: 99%

See 1 more Smart Citation

Revolutionizing Cancer Treatment: Unleashing the Power of Viral Vaccines, Monoclonal Antibodies, and Proteolysis-Targeting Chimeras in the New Era of Immunotherapy

Mohite,

Yadav,

Pandhare

et al. 2024

ACS Omega

Self Cite

View full text Add to dashboard Cite

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“…Nonetheless, a significant challenge associated with the application of PROTACs lies in ensuring their effective intracellular delivery. This challenge can be addressed with the use of exosomes as delivery vectors (Kar et al, 2023; Mukerjee, Maitra, Ghosh, et al, 2023; Mukerjee, Maitra, Gorai, et al, 2023; Sakamoto et al, 2001).…”

Section: Exosome‐mediated Protacs Delivery In Influenza a H3n2 Varian...mentioning

confidence: 99%

“…The use of exosomes in drug delivery, particularly for the targeted delivery of PROTACs (Mukerjee et al, 2023), represents a significant advancement in therapeutic technology, focusing on their innate attributes that make them suitable for drug delivery, methods to enhance targeting and delivery, and techniques to load PROTACs into exosomes effectively (Figure 3).…”

Section: Exosome‐mediated Protacs Delivery In Influenza a H3n2 Varian...mentioning

confidence: 99%

Proteolysis‐targeting chimeras in antiviral therapy: Leveraging influenza virus and exosome‐mediated delivery for targeted protein degradation and therapeutic advancements

Mukerjee,

Maitra,

Sharma

2024

Drug Development Research

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As the battle intensifies against the Influenza A-H3N2 variant, the need for groundbreaking strategies is evident. Globally, the prevalence of influenza, a zoonotic viral respiratory ailment, underscores this urgency. The H3N2 subtype, notorious for causing the 1968 Hong Kong Flu pandemic and the 2003 Fujian human flu, re-emerged in the United States in 2011, alarming health experts. Birthed from a complex triple-reassortment of human, swine, and avian influenza strains, including H1N1 and H1N2, its virulence and lethal nature are well-documented. Recent spikes of H3N2 cases in India, totaling 451 in the initial quarter alone, highlight the looming global health threat (Javanian et al., 2021; Taubenberger & Morens, 2008). Due to the flu virus's ever-changing nature, creating effective antivirals remains a challenge. However, a recent study heralds a potential gamechanger. The research presents a novel approach using exosomemediated delivery of proteolysis-targeting chimera (PROTACs) for precise protein degradation. Targeting key viral proteins, like hemagglutinin, neuraminidase, matrix protein, RNA-dependent RNA polymerase, and nucleoprotein, the study designs specific PROTAC ligands that impede viral replication. Envision exosomes

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Harnessing PROTACs to combat H5N1 influenza: A new frontier in viral destruction

Mukerjee,

Maitra,

Mukherjee

et al. 2024

Journal of Medical Virology

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H5N1, a highly pathogenic avian influenza virus, poses an ongoing and significant threat to global public health, primarily due to its potential to cause severe respiratory illness and high mortality rates in humans. Despite extensive efforts in vaccination and antiviral therapy, H5N1 continues to exhibit high mutation rates, resulting in recurrent outbreaks and the emergence of drug‐resistant strains. Traditional antiviral therapies, such as neuraminidase inhibitors and M2 ion channel blockers, have demonstrated limited efficacy, necessitating the exploration of innovative therapeutic strategies. Proteolysis‐targeting chimeras (PROTACs) emerge as a novel and promising approach, leveraging the ubiquitin‐proteasome system to selectively degrade pathogenic proteins. Unlike conventional inhibitors that only block protein function, PROTACs eliminate the target protein, providing a sustained therapeutic effect and potentially reducing the development of resistance. This paper offers a comprehensive examination of the current landscape of H5N1 infections, detailing the pathogenesis and challenges associated with existing treatments. It further explores the mechanism of action, design, and therapeutic potential of PROTACs in inhibiting H5N1. By targeting essential viral proteins, such as hemagglutinin and the RNA‐dependent RNA polymerase complex, PROTACs hold the potential to revolutionize the treatment of H5N1 infections, offering a new frontier in antiviral therapy.

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Revolutionizing Human papillomavirus (HPV)‐related cancer therapies: Unveiling the promise of Proteolysis Targeting Chimeras (PROTACs) and Proteolysis Targeting Antibodies (PROTABs) in cancer nano‐vaccines

Cited by 8 publications

References 21 publications

Revolutionizing Cancer Treatment: Unleashing the Power of Viral Vaccines, Monoclonal Antibodies, and Proteolysis-Targeting Chimeras in the New Era of Immunotherapy

Revolutionizing Cancer Treatment: Unleashing the Power of Viral Vaccines, Monoclonal Antibodies, and Proteolysis-Targeting Chimeras in the New Era of Immunotherapy

Proteolysis‐targeting chimeras in antiviral therapy: Leveraging influenza virus and exosome‐mediated delivery for targeted protein degradation and therapeutic advancements

Harnessing PROTACs to combat H5N1 influenza: A new frontier in viral destruction

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