Application of CD19-CART cells in B-cell lymphocytic leukemia

Application of CD19-CART cells in B-cell lymphocytic leukemia
CD19 CART cells can recognize specific CD19 targets of B-cell lymphocytic leukemia. By
releasing cytokines such as perforin and granzymes, CD19-CART cells attack the B lymphocytes
expressing CD19 antigen, thereby prompting the body to eliminate malignant lymphocytes. The
US Sloan-Kettering Cancer Center applied autologous 19-28z CART in the treatment of refractory
and relapsed B-ALL. Fourteen of the 16 patients had CR and were even effective in relapsed Ph+
ALL after transplantation. Treatment with CART also creates conditions for allogeneic
hematopoietic stem cell transplantation. The University of Pennsylvania also reported the use of
19-CD137zCART for the treatment of B-cell tumors. Thirty patients with refractory and relapsed
B-ALL and 27 patients achieved CR. The 6-month disease-free survival rate was 67%, and the
overall survival rate was 78%.
Brenyjens et al. used the second CAR T generation, CD19-specific CART cells transfected with
CD28/CD3-ζ, to treat 5 patients with relapsed B-ALL. The number and function of CART cells
were detected by PCR sequencing. The results showed that CART cells could rapidly produce
anti-tumor effects in vivo, and the detection of minimal residual disease turned to negative soon
and reached CR. Grupp et al. reported CR in 2 patients with refractory and relapsed B-ALL
treated with 2nd generation CART cells. One of them was relapsed after umbilical cord blood
allogeneic hematopoietic stem cell transplantation and had dual specificity for CD3 and CD19.
The monoclonal antibody blinatumomab is resistant. Second-generation CART cells containing 4-
1BB produced by lentiviral vector transfection technique, the number of infused T cells was
(1.4×106-1.2×107)/kg, T cell proliferation was more than 1000 times, and peripheral blood was 2
weeks after infusion. Both lymphocytes and neutrophils were significantly elevated. The
lymphocytes were mainly T cells, especially CART cells. CART cells can also be present at high
levels in the cerebrospinal fluid for at least 6 months, while 2 patients do not have central nervous
system leukemia, indicating the prevention and treatment of CART cells for central nervous
system leukemia. The main adverse reactions were agranulocytosis, fever, hypotension, acute
vascular leak syndrome, acute respiratory distress syndrome, elevated ALT and AST, and no acute
toxicity.
At the 56th ASH Conference in 2015, Novartis announced the latest clinical data of the industryrequired
CART immunotherapy CTL019. Thirty-nine children with relapsed and refractory ALL
received CD19-CART cell therapy, and 92% (36/39) achieved CR during the follow-up period of
6 months; 69% (27/39) were in continuous remission and the overall survival rate was 74%
(29/39). In a study of 24 cases of CLL treated with CD19 CAR T cells, 50% (12/24) achieved CR;
at a follow-up of 9 months, the overall survival rate was 67% (16/24).
At the 2013 ASH meeting, the University of Pennsylvania at the United States announced their
latest clinical research results. 14 patients with relapsed and refractory CLL were treated with
CART cells. The median number of CART cells transfused was 1.4×108(0.14×108~5.90×108).
As of July 15, 2013, the median follow-up time for all patients was 9.4 (4 to 35) months, and
effective patients were 16 (5 to 35) months. The results showed that 8 out of 14 patients were
effectively treated. Among them, 3 patients achieved CR. All patients were followed up for 11, 34,
and 35 months without recurrence. Five patients achieved PR and 2 of them appeared after 4
months of infusion. relapse.
A phase II study at the University of Pennsylvania was reported at the 2013 ASH conference to

find out the optimal number of CART cells for anti-tumor effects. In this study, 10 patients with
relapsed and refractory CLL were enrolled. All patients were treated with CART cells, of whom 6
were treated with low amounts (5×107) and 4 patients were treated with high amounts (5×108).
The median follow-up was 3 months. There was no significant difference in the efficacy and
adverse reactions between the two groups.
The use of CART cells to specifically target CD19-positive B-cell lymphoma and leukemia
patients has achieved significant clinical efficacy and is expected to be widely used. Although the
current CART treatment is carried out for a short period of time, there is still a lack of large-scale
samples, and many adverse reactions and complications need to be gradually discovered and
resolved in clinical trials. However, in the clinical trials reported for the treatment of B-cell
lymphoma and leukemia, CART showed a very significant effect, especially for relapsed and
refractory patients, thus providing a basis for a larger-scale, multi-center clinical study.
Author Bio
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