Introduction to PBMC for cell immunotherapy
PBMC is an abbreviation for peripheral blood mononuclear cells. Note that here is the mononuclear cell, not the Monocyte monocyte, which refers to any peripheral blood cell that has a rounded nucleus. That is to say, PBMC is an immune lymphocyte derived from the blood of healthy animals.
These cells include lymphocytes (T cells, B cells, NK cells) and monocytes, and granulocytes (including neutrophils, basophils, and eosinophils) have multi-lobed nuclei, sometimes it is divided into this category [1].
Therefore, PBMC is not a kind of cell, but a mixed immune cell. And immune cells are the most important soldiers in the body against viral diseases. Lymphocytes, monocytes, and Neutrophil Granulocytes in PBMC have very strong anti-tumor (cancer cells) and anti-viral effects!
However, T cells and NK (Natural Killer) cells are most important lymphoid in PBMC.
免疫療法的時代即將到來（這篇主要講的是T細胞，PBMC擁有更廣泛的應用範圍），免疫療法不單單對腫瘤有幫助，也可以幫助各種病毒感染疾病。
免疫療法改變了肺癌治療的前景，為晚期肺癌患者帶來了希望。 免疫療法通過激活患者的免疫系統，幫助它更好地對抗和破壞癌細胞起作用。 癌細胞通過表達PD-L1（程序性死亡配體1）逃避T細胞的死亡，然後通過與T細胞表面上的PD-1（PDCD1）結合使T細胞失活。 免疫療法靶向PD-1（PDCD1）或PD-L1，阻止腫瘤抑制T細胞並使T細胞殺死癌細胞。
To improve the effect of cell therapy, chimeric antigen receptor T cells (also known as CAR T cells) or CAR NK cells are applied, which are T / NK cells that have been genetically engineered to produce an artificial cell receptor.
Chimeric antigen receptors are bioengineered proteins that give T-cells the mechanism to neutralize a particular protein. The receptors are termed "chimeric" because they utilize both native T-cell functions and the new antigen-recognizing functions into one receptor.
CAR-T cell therapy uses T cells engineered with CARs for cancer therapy. The premise of CAR-T immunotherapy is to modify T cells to recognize cancer cells in order to more effectively target and destroy them. Scientists harvest T cells from people, genetically alter them, then infuse the resulting CAR-T cells into patients to attack their tumors [1]. CAR-T cells can be either derived from T cells in a patient's own blood (autologous) or derived from the T cells of another healthy donor (allogenic). Once isolated from a person, these T cells are genetically engineered to express a specific CAR, which programs them to target an antigen that is present on the surface of tumors. For safety, CAR-T cells are engineered to be specific to an antigen expressed on a tumor that is not expressed on healthy cells [2].
After CAR-T cells are infused into a patient, they act as a "living drug" against cancer cells.[3] When they come in contact with their targeted antigen on a cell, CAR-T cells bind to it and become activated, then proceed to proliferate and become cytotoxic.[4] CAR-T cells destroy cells through several mechanisms, including extensive stimulated cell proliferation, increasing the degree to which they are toxic to other living cells (cytotoxicity), and by causing the increased secretion of factors that can affect other cells such as cytokines, interleukins, and growth factors.[5]
In the year of 2017, FDA approved two CAR-T therapies both target the CD19 antigen, which is found on many types of B-cell cancers.[6] Tisagenlecleucel (Kymriah) is approved to treat relapsed/refractory B-cell precursor acute lymphoblastic leukemia (ALL), while axicabtagene ciloleucel (Yescarta) is approved to treat relapsed/refractory diffuse large B-cell lymphoma (DLBCL).[6]
We HKADRF are actively preparing for CAR-T & CAR-NK related research projects for pet dogs and cats, hoping to get your financial support.
Reference:
- Fox, Maggie (July 12, 2017). "New Gene Therapy for Cancer Offers Hope to Those With No Options Left". NBC News.
- Srivastava S, Riddell SR (August 2015). "Engineering CAR-T cells: Design concepts". Trends in Immunology. 36 (8): 494–502. doi:10.1016/j.it.2015.06.004. PMC 4746114. PMID 26169254.
- Sadelain M, Brentjens R, Rivière I (April 2013). "The basic principles of chimeric antigen receptor design". Cancer Discovery. 3 (4): 388–98. doi:10.1158/2159-8290.CD-12-0548. PMC 3667586. PMID 23550147.
- Hartmann J, Schüßler-Lenz M, Bondanza A, Buchholz CJ (2017). "Clinical development of CAR T cells-challenges and opportunities in translating innovative treatment concepts". EMBO Molecular Medicine. 9 (9): 1183–1197. doi:10.15252/emmm.201607485.
- Tang XJ, Sun XY, Huang KM, Zhang L, Yang ZS, Zou DD, Wang B, Warnock GL, Dai LJ, Luo J (December 2015). "Therapeutic potential of CAR-T cell-derived exosomes: a cell-free modality for targeted cancer therapy". Oncotarget. 6 (42): 44179–90. doi:10.18632/oncotarget.6175. PMC 4792550. PMID 26496034.
- "Thumbs Up to Latest CAR T-Cell Approval". www.medpagetoday.com. 2017-10-19.
以下全文轉載自東周網2018年12月16日發佈的文章
PD-1免疫治療在2011年開始在人類治療癌症中應用，李恆年獸醫認為其治療原理如剎車系統。PD-1其實是一種細胞外層的蛋白質，它原本的功能是讓免疫系統不攻擊某些良好細胞，但是腫瘤會偽裝成良好的細胞，發放出PDL-1這種細胞與PD-1結合，利用PD-1的特色讓免疫系統中的T細胞不能正常殺死腫瘤。