Recently, scientists at the University of Pennsylvania and Novartis reported that CD-19-CAR T cell therapy got the expected results in an early CD19 CAR-T preclinical assay involving 43 patients with non-Hodgkin’s lymphoma. These subjects were all patients with chemotherapy failure and expected survival of only about 3 months. These chemotherapy regimens include Rituximab, an antibody (first-line therapy) with B-cell antigen CD20 as the drug target. However, only 30 of the 43 subjects were successfully administered, and other patients failed to receive CD19-CAR T cell therapy due to CAR-T cell preparation failure. Among the patients successfully treated, 15 were diffuse large B cell lymphoma, 13 were folicular lymphoma, and 2 were mantle cell lymphoma.
At present the clinical trial has been carried out for about two years, and the total response rate is 47%. Six of the patients have got completely remission, and one of them did not be seen tumor recurrence in 14 months of observation. The CD19 CAR T cell therapy was most effective in follicular lymphoma with a response rate of 73%. Side effects were also expected, with only one case of lethal encephalitis, and the primary side effects were cytokine release storm (but mostly one to two level) and reversible nervous system toxicity.
CD19 is a transmembrane glycoprotein with a molecular weight of 95 kDa. Although the vast majority of CD19 are expressed on the surface of B cells, Anti-CD19 CAR T is not a traditional anti-tumor molecular target. Because an anti-tumor molecular target is usually a cancer driver gene, and the mutation of the gene leads to tumorigenesis, so inhibition of it have the function of anti-cancer. Of course, this gene is very few. The current found oncogenes are mostly tumor-related genes. And for known carcinogens, such as BCR-ABL, Her-2, FGFR, Braf, ENL-4-ALK, PI3K and MET2, there have been listed drugs. The CD-19 is a B cell receptor, which is not related to the tumor occurrence, but surprisingly, turns out to be a very good drug target, and almost becomes a synonym for the success of CAR-T.
The earliest and the biggest success CAR T cell therapy is acute lymphoblastic leukemia (ALL). ALL is a B cell T cell precursor cell (lymphoblastoid) -based blood cancer. With the involvement of bone marrow transplantation, ALL cure rate has been quite high, and almost ninety percent of the sick children can be cured. But 10% of the patients will die due to resistance. In response to these recurrent and refractory ALL patients, CD19-CAR T cell therapy is also very surprising. After treatment, in the blood of more than 90% patients has not been detected cancer cells.
Chronic lymphocytic leukemia (CLL) cancer cells are also B cells. CD19 has a good expression in B cells, so CD19-CAR T cell therapy is also quite good in CLL clinical efficacy with 45% response rate in patients of chemotherapy failure. Some of them survive for four years.
Non-Hodgkin’s Lymphoma is also a B-cell tumor. CD-19-CAR T is also effective because B cells express CD19. Although the above clinical trial is short and the number of samples is not large (43 cases), the reported information is very positive in the effect. Since both of these diseases are associated with B cells, and all express CD-19, so CD-19-CAR T cell therapy is effective. Although the above clinical trials use the CD19 CAR product from University of Pennsylvania and Novartis, I believe results of Juno, Blue birds and Kite will be roughly the same. CD-19 is a preferred target for CAR-T therapy with a non-oncogenic gene.
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