Harnessing immunotherapy: cancer vaccines as novel therapeutic strategies for brain tumor

Abstract

Cancer vaccines have emerged as a pivotal area of research in oncology, demonstrating significant promise in harnessing the immune system to combat cancer. Recent advancements in antigen identification and sequencing techniques have catalyzed the development of cancer vaccines whose goal is to elicit robust humoral and cellular immune responses against cancer cells. Despite their potential, most cancer vaccines are still in the experimental phase, primarily due to challenges associated with tumor-induced immune suppression. This article explores the role of cancer vaccines in brain cancer, glioblastoma, by providing a granular analysis of clinical trial results and mechanisms of resistance alongside a comparative assessment. These vaccines aim to navigate the immunosuppressive tumor microenvironment by targeting glioblastoma-specific antigens, offering new hope for improved treatment outcomes. The unique mechanisms defining cancer vaccines, such as their ability to activate dendritic cells and T cells, underscore their precision in selectively attacking cancer cells while sparing healthy tissue. Furthermore, the categorization of these vaccines into preventive and therapeutic types, along with various delivery methods, illustrates their diverse capacity. Finally, this review highlights the potential impact of cancer vaccine clinical trials on future cancer therapies, where effective anti-cancer strategies are within reach. It also provides an in-depth discussion of the brain tumor microenvironment and its influence on vaccine efficacy.

Keywords: brain tumor; cancer vaccine; glioblastoma; immunotherapy; vaccine.

Figure 1

Developing cancer vaccines for glioblastoma patients in clinical trials follows a structured process designed to stimulate an immune response. In addition to conventional administration routes, such as intramuscular, subcutaneous, or injection into the post-surgical tumor cavity, some approaches involve a more complex preparation process. It begins with harvesting a tumor sample during surgery, from which cancer cells are isolated or processed into a tumor lysate rich in tumor-specific antigens. Simultaneously, white blood cells are collected from the patient and differentiated into antigen-presenting cells (APCs), specifically DCs. Tumor antigens are thus either loaded onto DCs or fused with them to create hybrid DCs capable of effectively presenting tumor-associated antigens ex vivo. Once activated, these DCs are reintroduced into the patient as a vaccine, aiming to trigger a robust immune response against the tumor.

Figure 2

Upon administration, the vaccine initiates an immune cascade. APCs, such as DCs, recognize and process the introduced tumor antigens at the site of injection. These cells present the processed antigens on their Major Histocompatibility Complex (MHC) molecules to immune effectors, including natural killer (NK) cells and CD4+ and CD8+ T cells. The activated T cells proliferate and secrete cytokines, thereby amplifying the immune response by recruiting additional immune cells, such as M1 macrophages and B cells. These activated immune cells circulate throughout the body, seeking out and attacking tumor cells. However, glioblastoma presents significant challenges, such as the BBB and an immunosuppressive tumor microenvironment, which limit immune cell infiltration and function, ultimately contributing to immune evasion and continued tumor growth.

Figure 3

Timelines of milestones in cancer immunotherapy, including glioblastoma, provide a chronological overview of significant developments and achievements.

Figure 4

Challenges in glioblastoma treatment. Glioblastoma poses a challenge for immunotherapy due to its limited immunogenicity, primarily affected by the BBB and the immunosuppressive TME. The BBB restricts the entry of therapeutic agents into the brain, making it challenging to deliver immunotherapy to the tumor site. Additionally, the TME organizes an immunosuppressive environment, protecting GSCs from recognition and immune attack. They also often mimic their antigens, avoiding detection and removal by the immune system. Moreover, they recruit immunosuppressive cells, such as MDSCs and Treg cells, and secrete immunosuppressive cytokines, which inhibit the activation and function of immune cells.

Figure 5

Key components of cancer vaccines.