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At the bench: Engineering the next generation of cancer vaccines
Daniel Shae1, Jessalyn J Baljon2, Mohamed Wehbe1
1Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, Tennessee, USA.
Abstract:
Cancer vaccines hold promise as an immunotherapeutic modality based on their potential to generate tumor antigen-specific T cell responses and long-lived antitumor responses capable of combating metastatic disease and recurrence. However, cancer vaccines have historically failed to deliver significant therapeutic benefit in the clinic, which we maintain is due in part to drug delivery challenges that have limited vaccine immunogenicity and efficacy. In this review, we examine some of the known and putative failure mechanisms of common first-generation clinical cancer vaccines, and describe how the rational design of materials engineered for vaccine delivery and immunomodulation can address these shortcomings. First, we outline vaccine design principles for augmenting cellular immunity to tumor antigens and describe how well-engineered materials can improve vaccine efficacy, highlighting recent innovations in vaccine delivery technology that are primed for integration into neoantigen vaccine development pipelines. We also discuss the importance of sequencing, timing, and kinetics in mounting effective immune responses to cancer vaccines, and highlight examples of materials that potentiate antitumor immunity through spatiotemporal control of immunomodulation. Furthermore, we describe several engineering strategies for improving outcomes of in situ cancer vaccines, which leverage local, intratumoral delivery to stimulate systemic immunity. Finally, we highlight recent innovations leveraging nanotechnology for increasing the immunogenicity of the tumor microenvironment (TME), which is critical to enhancing tumor infiltration and function of T cells elicited in response to cancer vaccines. These immunoengineering strategies and tools complement ongoing advances in cancer vaccines as they reemerge as an important component of the immunotherapeutic armamentarium.
Insights
Cancer vaccines show promise but face delivery challenges. Engineered materials can enhance immunogenicity and efficacy for better antitumor responses, improving cancer immunotherapy outcomes.
Area of Science:
- Immunology
- Materials Science
- Oncology
Background:
- Cancer vaccines aim to elicit T cell responses against tumors, but clinical success is limited by drug delivery issues impacting immunogenicity and efficacy.
- First-generation cancer vaccines often fail due to suboptimal delivery, hindering their potential for long-lived antitumor immunity against metastatic disease.
Purpose of the Study:
- To review failure mechanisms of current cancer vaccines and explore how engineered materials can improve their immunogenicity and therapeutic efficacy.
- To highlight innovations in materials science for rational vaccine design, focusing on enhancing cellular immunity, spatiotemporal control of immunomodulation, and in situ vaccination strategies.
Main Methods:
- Review of existing literature on cancer vaccine failures and materials-based delivery systems.
- Analysis of engineering strategies for optimizing vaccine immunogenicity, including nanotechnology and spatiotemporal control of immune responses.
- Discussion of in situ vaccination approaches and their potential to stimulate systemic immunity.
Main Results:
- Engineered materials can overcome delivery challenges, significantly boosting cancer vaccine immunogenicity and efficacy.
- Rational design principles and advanced delivery technologies, including nanotechnology, can enhance T cell responses and antitumor immunity.
- Spatiotemporal control of immunomodulation and in situ vaccination strategies show promise for improving treatment outcomes.
Conclusions:
- Materials engineering offers solutions to enhance cancer vaccine performance by improving delivery, immunogenicity, and efficacy.
- Innovations in immunoengineering and nanotechnology are crucial for advancing cancer vaccines as a key component of cancer immunotherapy.
- Addressing delivery and immunomodulation challenges through rational design is essential for realizing the full therapeutic potential of cancer vaccines.
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