In the article Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors, published in 2020, cord blood was used as a source of lymphocyte cells as a treatment for a specific cancer type. The cancer type targeted were CD19-positive cancers, like non-Hodgkin\u2019s lymphoma (NHL) or chronic lymphocytic leukemia [CLL] (Enli, Liu. Et al., 2020). Clusters of differentiation (CD) are immunological markers that specify a transmembrane protein that is expressed on B-cells. Non-Hodgkin\u2019s lymphoma arises from a malignancy in these lymphocytes, that in early stages of development have these CD19 markers (Raufi, Ali., Shukkur-Ebrahim, Abdul., Al-Katib, Ayad., 2013).<\/p>\n\n\n\n
In the study described in the article, anti-CD19 natural killer (NK) type T-cells were genetically engineered from the cord blood into an injectable serum. Natural killer (NK) cells are a subclass of T-cell lymphocytes that destroy infected or diseased cells, like cancer cells (\u201cNatural Killer Cells,\u201d 2023). The serum was manufactured by purifying NK cells from the blood sample and placing them in a culture with specific growth factors with desired properties for the study. The cells\u2019 genetic information was targeted for anti-CD19 receptors and encoded using a retroviral vector to encode the information. It was demonstrated that 100 doses of the NK cells could be derived from a single cord blood unit (Enli, Liu. Et al., 2020).<\/p>\n\n\n\n
The study was performed through the University of Texas M.D. Anderson Cancer Center. There were 11 participants that completed the duration of the experiment. The patients followed a pre-infusion regiment of chemotherapy and medication in preparation for the trial. The participants also underwent HLA genotyping (Enli, Liu. Et al., 2020). Human leukocyte antigen (HLA) is a type of cell surface molecule that contributes to the body\u2019s immune response. HLAs differ amongst individuals and is determined by their specific genotype. Testing for HLAs is done to ensure the transplantation or transfusion of biological material from another patient does not trigger an immune response against the introduced material (\u201cHuman Leukocyte Antigen,\u201d 2024). In the study, the first nine patients received a NK product that was partially matched with the HLA genotype of the recipient. The last two patients were given a NK product with no consideration for HLA matching, but instead had a mismatch in genes that code for the chimeric antigen receptors (CARs) used to redirect the specificity of the desired NK T-cells. There were no observable instances of graft-versus-host-disease, despite the HLA mismatch (Enli, Liu. Et al., 2020).<\/p>\n\n\n\n
The conclusion of the study saw at a follow up of 13.8 months, 73% of participants had an objective response to the treatment, and 64% had a complete response in terms of enhanced proliferation and persistence of the transduced cells. While naturally derived NK cells last only two weeks in the body, the derived CAR-NK cells had persistence levels of at least 12 months. Participants had a one-year progression-free survival of around 30% of patients with CLL and 45% among those with NHL. The efforts of the study demonstrated that derived anti-CD19 CAR NK cells can be administered to people suffering from CD19 positive cancers without mounting an immunological response, and that those foreign cells can proliferate and target developing cancer cells for destruction (Enli, Liu. Et al., 2020).<\/p>\n\n\n\n
References<\/p>\n\n\n\n
Enli, Liu. Et al. Use of CAR-transduced natural killer cells in CD19-positive lymphoid tumors. New England Journal of Medicine; https:\/\/doi.org\/10.1056\/NEJMoa1910607<\/a> (2020).<\/p>\n\n\n\n Raufi, Ali., Shukkur-Ebrahim, Abdul., Al-Katib, Ayad. Targeting CD19 in B-cell lymphoma: emerging role of SAR3419. NIH. 10.2147\/CMAR.S45957<\/a> (2013).<\/p>\n\n\n\n Natural Killer Cells. (2023). https:\/\/my.clevelandclinic.org\/health\/body\/24898-natural-killer-cells<\/a><\/p>\n\n\n\n