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Cancer vaccine is the next big thing in medulloblastoma treatment: here's why?

Cancer immunotherapy is one of the most promising and fastest-growing areas in cancer research and treatment. Immunotherapy is a type of cancer treatment that uses the body’s immune system to fight cancer cells. Cancer vaccines are different from traditional vaccines because they are specifically designed to target cancer cells. The goal of cancer vaccines is to stimulate the immune system to recognize and destroy cancer cells [1].

Need for a cancer vaccine for medulloblastoma

The potential side effects and long-term toxicities of the existing therapies used to treat medulloblastoma (MB), which typically involves surgery, radiation, and chemotherapy, cause a huge burden on patients and their families. Minimizing these undesirable outcomes without affecting the effectiveness of treatment is the effort of cancer immunotherapy. It aims to lower the doses of cytotoxic agents and radiation, along with the optimization of overall survival. Recent advances in cancer immunotherapy have led to the development of cancer vaccines that can be used to treat a wide range of cancers, including MB [2].

How do cancer vaccines work?

Cancer vaccines can consist of whole tumor cells, peptides, DNA, and RNA, and that target the cancer-tolerating immune system. Cancer vaccines that use whole tumor cells and peptides deliver efficient tumor antigens directly to antigen-presenting cells (APCs). These APCs will present the antigen as epitopes on the surface of their own MHC class I and II molecules, followed by recognition by T cells. In contrast, for the DNA- and RNA-based cancer vaccines, genes need to be transcribed or translated into proteins in host cells before being presented or recognized, for creating personalized antigens that can be presented to APCs to elicit an immune response. Cancer vaccines are an exciting and promising new frontier in cancer treatment and have the potential to dramatically improve the outlook for people with cancer [1], [2].

Does a cancer vaccine exist to treat MB?

The number of patients with MB has increased during the past decades. Although there is no known reason for this rise, researchers have been working constantly to develop a strategy to prevent and treat MB. Cancer vaccine in MB can be an uncommon instance, despite substantial advancements and promising clinical outcomes found in cancer vaccination trials. Recent clinical trials with MB patients have tested a variety of cancer vaccines, but none of them have been able to significantly boost T-cell responses. This is caused, at least in part, by the scarcity of viable tumor tissue that can be used to make tumor cell-based vaccine preparations and the difficulty in identifying tumor-specific antigens that are consistently expressed in these tumors.

Are there any challenges in treating mb patients with the cancer vaccine?

The milieu around MB tumors is not particularly immunogenic. Hypoxia, a low extracellular pH, and high interstitial fluid pressure are all related to the MB tumor microenvironment, which makes drug distribution and effectiveness more difficult. Thus, future versions of an MB cancer vaccine must overcome tumor antigen heterogeneity and tumor immunosuppressive mechanisms. Additionally, the blood-brain barrier still presents a significant obstacle to the treatment of brain cancers like MB. Due to their size, IgG antibodies have poor blood-brain barrier penetration. Molecules greater than 500 Da cannot pass across the blood-brain barrier due to tight junctions of epithelial cells. Moreover, it has been shown that CAR T cells can cross the blood-brain barrier, especially when coupled to peptides with fewer than 40 residues that are capable of transcytosis. Thus, to cross the blood-brain barrier, cell-penetrating peptides may be combined with vaccinations or antibody treatments. Furthermore, several variables may make it challenging for the immune system also to identify and destroy cancer cells that are growing:

Since many cancer-associated antigens are slightly modified versions of self-antigens, the immune system may have trouble identifying them.
Larger or more advanced tumors are hard to get rid of using only a vaccine.
Cancer cells may experience genetic alterations that may result in the loss of cancer-associated antigens [2], [3].

Are there any challenges in treating mb patients with the cancer vaccine?

Although it is too early to decide the long-term safety of a cancer vaccine for the treatment of patients with MB, primary results indicate that these vaccines are well-tolerated and may in turn help to increase the survival and quality of life. Activating an anti-tumor immune response is crucial because it creates the foundation for the iterative development of cancer vaccines that can effectively treat people with MB. There are some challenges associated with the use of cancer vaccines to treat MB, hence in the future, more clinical trials are necessary to decide the long-term safety of cancer vaccines. Preclinical research must be devised to detect new antigen targets and develop treatments that can target several antigens at the same time. Combination therapy should be the standard of care for MB in the future to enhance survival rates by combating tumor immunosuppression and triggering immunity via vaccines.

Key memorandum

Both adult and pediatric MB patients frequently experience impairment in the treatment-related quality of life, highlighting the necessity for precision medical remedies that preserve the viability and functions of the surrounding tissues.
The rapid development of cancer immunotherapy raises the possibility of targeted removal of malignant cells while maintaining healthy tissues.
Improvements in immunotherapeutic approaches can be made by concentrating on strategies that trigger anti-tumor immunity, rather than just relying on the elimination of neo-epitopes [1], [2].