Wikipedia

Draft:B-cell therapy for tumors

B cells are a subtype of white blood cells that play a crucial role in the immune system [1]. When memory B cells encounter antigens (such as bacteria or viruses), they proliferate and differentiate into plasma cells, becoming effector cells that secrete antibodies [2]. Each plasma cell operates like a factory, constantly producing antibodies [3]. B cells express B cell receptors (BCRs) on their cell membranes, which enables them to bind to foreign antigens and initiate antibody reactions [4]. These BCRs have high specificity, and all BCRs on a single B cell recognize the same protein epitope [5]. The interaction between antibodies and antigens can be likened to a key in a lock. When antibodies and antigens interlock, antigens (bacteria or viruses) are disrupted [6]. Due to the ability of B cells to produce neutralizing antibodies, the potential of these antibodies in the treatment of various diseases, including cancer, has been widely studied [7][8]. Neutralizing antibodies can bind to surface proteins of cancer cells. The therapeutic mechanism includes their interaction with cancer cell receptors, blocking the connection between cancer cells and proteins that stimulate cell growth, which is a key process for cancer growth and survival. Neutralizing antibodies can also activate certain signaling pathways, leading to cell death or apoptosis [9][10]. Understanding these is crucial for the development of B-cell immunotherapy for tumors.

Dr. Zheng Liu from Guilin Medical University has developed an innovative cancer treatment strategy that activates B cells to produce specific neutralizing antibodies against tumors [11]. The working principle of this method is based on the following scientific understanding. The formation of tumors is a complex process. When tumor cells begin to grow in a healthy body, they gradually adapt and evade immune surveillance. Once the number of tumor cells exceeds a specific threshold, the tumor will begin to form [12]. During this process, proteins within tumor cells accumulate various mutations to adapt to the body's immune system and the microenvironment surrounding the tumor, thereby avoiding recognition by the body as foreign objects and triggering immune responses [13]. Due to the exposure of different mutated protein epitopes on the surface of tumor cells at different stages of development, and sometimes even random exposure of mutated protein epitopes, there may be tumor cells in different stages of development, different types of mutated proteins, and different mutated epitopes of the same protein within a tumor [14]. However, current targeting drugs for tumor therapy are mainly developed for a specific mutation epitope in tumor cells at a certain stage [15]. This leads to the ineffectiveness of targeted drugs against other mutated proteins and epitopes, which is also the main reason for drug treatment failure and tumor recurrence [16].

The function of B cells is to produce antibodies, which can kill bacteria or viruses through antigen antibody immune reactions [17]. Mutated proteins in tumor cells are abnormal for other normal and healthy organisms, just like sudden viruses that are easily detected. Based on the above principles, Dr. Zheng Liu proposed targeted treatment of tumors by stimulating B cells to produce specific homologous antibodies [18]. This method involves inputting tumor cells from different stages of mice into the body of healthy mice, producing specific homologous antibodies targeting different stages of mutated proteins or different epitopes of mutated proteins, and then reintroducing them back into the body of tumor mice, gradually killing tumor cells until they fall below the threshold, and finally completely eliminating the tumor. This method takes mouse squamous cell carcinoma (mCSCC) as an example. The experiment is divided into three stages:

1. Cells isolation and culture: Separate and culture mCSCC cells from mCSCC.

2. Antibody production: mCSCC cultured and expanded tumor cells are injected into healthy mice to produce homologous neutralizing antibodies against tumor mCSCC.

3. Serum therapy: Collect serum from healthy mice and transfuse it back into tumor mice to kill tumor cells.

This tumor treatment method is very effective in treating mouse mCSCC. The research findings were published in the eLife journal on April 16, 2024, with the title "Generating specific homologous neutralizing antibiotics: a novel therapeutic strategy in cancer treatment”. In the future, further in-depth research is needed to determine whether other tumor cells can be isolated, cultured, and then reintroduced to produce specific homologous antibodies for the purpose of treating tumors, and how this method can be applied to the human body. However, this innovative theory and methodology of B-cell immunotherapy for tumors have pioneered a new field in cancer treatment and unveiled fresh possibilities for combating cancer.

References

  1. ^ Tobón GJ, Izquierdo JH, Cañas CA. B lymphocytes: development, tolerance, and their role in autoimmunity-focus on systemic lupus erythematosus. Autoimmune Dis. 2013;2013:827254. doi: 10.1155/2013/827254.
  2. ^ Ionescu L, Urschel S. Memory B Cells and Long-lived Plasma Cells. Transplantation. 2019 May;103(5):890-898. doi: 10.1097/TP.0000000000002594.
  3. ^ Calame KL. Plasma cells: finding new light at the end of B cell development. Nat Immunol. 2001 Dec;2(12):1103-8. doi: 10.1038/ni1201-1103.
  4. ^ Heesters BA, van der Poel CE, Das A, Carroll MC. Antigen Presentation to B Cells. Trends Immunol. 2016 Dec;37(12):844-854. doi: 10.1016/j.it.2016.10.003.
  5. ^ Rodríguez-Pinto D. B cells as antigen presenting cells. Cell Immunol. 2005 Dec;238(2):67-75. doi: 10.1016/j.cellimm.2006.02.005.
  6. ^ Schindler L W. The immune system: How it works[M]. US Department of Health and Human Services, Public Health Service, National Institutes of Health, 1993.
  7. ^ Lu RM, Hwang YC, Liu IJ, Lee CC, Tsai HZ, Li HJ, Wu HC. Development of therapeutic antibodies for the treatment of diseases. J Biomed Sci. 2020 Jan 2;27(1):1. doi: 10.1186/s12929-019-0592-z.
  8. ^ Narang A S, Desai D S. Anticancer drug development: Unique aspects of pharmaceutical development[J]. Pharmaceutical perspectives of cancer therapeutics, 2009: 49-92.
  9. ^ Petit AM, Rak J, Hung MC, Rockwell P, Goldstein N, Fendly B, Kerbel RS. Neutralizing antibodies against epidermal growth factor and ErbB-2/neu receptor tyrosine kinases down-regulate vascular endothelial growth factor production by tumor cells in vitro and in vivo: angiogenic implications for signal transduction therapy of solid tumors. Am J Pathol. 1997 Dec;151(6):1523-30.
  10. ^ Roy DG, Bell JC, Bourgeois-Daigneault MC. Magnetic targeting of oncolytic VSV-based therapies improves infection of tumor cells in the presence of virus-specific neutralizing antibodies in vitro. Biochem Biophys Res Commun. 2020 Jun 4;526(3):641-646. doi: 10.1016/j.bbrc.2020.03.135.
  11. ^ Liu Zheng. Generating specific homologous neutralizing-antibodies: a novel therapeutic strategy in cancer treatment. 2024, eLife13:RP95678. https://doi.org/10.7554/eLife.95678.1
  12. ^ Zhu X, Li S, Xu B, Luo H. Cancer evolution: A means by which tumors evade treatment. Biomed Pharmacother. 2021;133:111016. doi: 10.1016/j.biopha.2020.111016.
  13. ^ Bozic I, Antal T, Ohtsuki H, Carter H, Kim D, Chen S, Karchin R, Kinzler KW, Vogelstein B, Nowak MA. Accumulation of driver and passenger mutations during tumor progression. Proc Natl Acad Sci U S A. 2010;107(43):18545-50. doi: 10.1073/pnas.1010978107.
  14. ^ Ebrahimi N, Akbari M, Ghanaatian M, Roozbahani Moghaddam P, Adelian S, Borjian Boroujeni M, Yazdani E, Ahmadi A, Hamblin MR. Development of neoantigens: from identification in cancer cells to application in cancer vaccines. Expert Rev Vaccines. 2022 Jul;21(7):941-955. doi: 10.1080/14760584.2021.1951246.
  15. ^ Zhong L, Li Y, Xiong L, Wang W, Wu M, Yuan T, Yang W, Tian C, Miao Z, Wang T, Yang S. Small molecules in targeted cancer therapy: advances, challenges, and future perspectives. Signal Transduct Target Ther. 2021 May 31;6(1):201. doi: 10.1038/s41392-021-00572-w.
  16. ^ Padma VV. An overview of targeted cancer therapy. Biomedicine (Taipei). 2015;5(4):19. doi: 10.7603/s40681-015-0019-4.
  17. ^ Lam JH, Smith FL, Baumgarth N. B Cell Activation and Response Regulation During Viral Infections. Viral Immunol. 2020 May;33(4):294-306. doi: 10.1089/vim.2019.0207.
  18. ^ Moffett HF, Harms CK, Fitzpatrick KS, Tooley MR, Boonyaratanakornkit J, Taylor JJ. B cells engineered to express pathogen-specific antibodies protect against infection. Sci Immunol. 2019 May 17;4(35):eaax0644. doi: 10.1126/sciimmunol.aax0644.
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