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Neoantigen vaccine for the treatment of liver cancer: a paradigm-shifting opportunity

One of the most promising and rapidly expanding fields of cancer research and treatment is cancer immunotherapy. The immune system of the body is activated during this therapy to combat cancer cells. Cancer vaccines work to activate this immune system so that it can find and eliminate cancer cells. The basic difference between conventional vaccines and cancer vaccines is that these vaccines are specifically created to target cancer cells. Neoantigen vaccine is one of the types of cancer vaccines that contains neoantigens specific to a particular tumor [1].


Is neoantigen vaccine required in liver cancer?


Liver Cancer

The current therapies used to treat liver cancer i;e surgery, radiotherapy, and chemotherapy impose a huge burden on patients due to their unavoidable side effects and long-term toxicities. Cancer immunotherapy makes an effort to reduce these unfavourable effects without compromising the effectiveness of treatment. The recent advances in cancer immunotherapy contributed to the development of neoantigen vaccines which are helpful in treating a variety of malignancies including liver cancer. Along with the improvement in overall survival, this vaccine can also reduce the dosage in radiotherapy and the drug dosage in chemotherapy [2].


How does the neoantigen vaccine help in liver cancer?


  • Cancer vaccines contain whole tumor cells, peptides, DNA, and RNA that target the immune system which tolerates cancer.

  • Neoantigen cancer vaccine contain neoantigens, which are novel peptides that are produced by rare scenarios such as gene mutation, alternative splicing, and virus integration in tumor cells. These neoantigens not only have a high level of immunogenicity but also have good tumor specificity. Therefore, the immune system in humans can easily recognize and combat these neoantigens.

  • These neoantigens (peptides) will effectively deliver the tumor antigens to antigen-presenting cells (APCs) in liver cancer.

  • The antigen will be displayed by these APCs as epitopes on the surface of their major histocompatibility complex (MHC) class I and II molecules, followed by T-cell recognition.

  • The idea of employing these detected neoantigens as vaccines to actively stimulate patient’s autoimmune system and elicit anti-tumor responses in liver cancer has received awareness in recent times.

  • Theoretically, compared to other types of immunotherapy, the neoantigen vaccine, a new type of tumor immunotherapy, can induce a strong specific immune response and elicit stable therapeutic effects in liver cancer [3].


Problems in treating liver cancer patients with neoantigen vaccine


Although the neoantigen cancer vaccine works effectively with the natural immune system of the host, there are a variable number of factors that are becoming challenging for the immune system to identify and eliminate the developing cancer cells:

  • The immune system cannot identify all the cancer-associated antigens as many of them are altered copies of self-antigens.

  • It is challenging to eradicate larger or more developed tumors with just a vaccination.

  • Cancer associated antigens may be gradually lost due to the genetic alterations that take place in the cancer cells [4].


Liver cancer and neoantigen: what should we remember?


Activating an anti-tumor immune response is crucial because it creates the foundation for the development of cancer vaccines that can effectively treat people with liver cancer. Primary results suggest that these vaccines are well-tolerated and may improve survival and quality of life. But further clinical trials are anticipated in the future to determine the long-term safety of neoantigen cancer vaccines for the treatment of patients with liver cancer.


The future of neoantigen vaccines should be directed towards improving its efficacy in overcoming tumor immunosuppressive mechanisms and antigen heterogeneity. Preclinical research must be carried out in order to identify new antigen targets and to create medications that can target several antigens simultaneously. Combination therapy (combining neoantigen vaccine with any of the conventional treatments) should be considered as a standard treatment in liver cancer to improve the overall survival rate [4].


References


1. M. Peng et al., Neoantigen vaccine: an emerging tumor immunotherapy,” Molecular Cancer, vol. 18, no. 1, p. 128, Aug. 2019, doi: 10.1186/s12943-019-1055-6.

2. D. Repáraz et al., Neoantigens as potential vaccines in hepatocellular carcinoma,” J Immunother Cancer, vol. 10, no. 2, p. e003978, Feb. 2022, doi: 10.1136/jitc-2021-003978.

3. P. Chen, Q.-X. Fang, D.-B. Chen, and H.-S. Chen, Neoantigen vaccine: An emerging immunotherapy for hepatocellular carcinoma,” World J Gastrointest Oncol, vol. 13, no. 7, pp. 673–683, Jul. 2021, doi: 10.4251/wjgo.v13.i7.673.

4. S.-Y. Ho et al., “Current Trends in Neoantigen-Based Cancer Vaccines,” Pharmaceuticals, vol. 16, no. 3, Art. no. 3, Mar. 2023, doi: 10.3390/ph16030392.

Comentários


Collaborators

IIT Guwahati
University of Manchester
Rhenix Lifesciences
American university of Sharjah
IIT Delhi
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