Anti-lymphocyte Tumor Mechanism of CD19-CART Cells

The Cytotoxic T cells are CD8+ T lymphocytes activated by antigen presenting cells
(APCs). Studies have shown that activation of T cells relies on activation of dual
signaling pathways to proliferate into cytotoxic T cells where the first signalling
pathway is the combination of the MHC molecule-antigenic peptide complex on
APCs and T cell receptors on T cells, and the second signaling pathway where the B7
co-stimulatory molecule on the APC surface binds to the CD28 molecule on the T cell
surface. When a cytotoxic T cell meets with a tumor cell carrying the same MHC
molecule-antigen peptide complex, release of perforin can result in cell lysis. In
addition, granzymes can be secreted to induce apoptosis in target cells.

The key to CAR T design is to select the appropriate tumor antigen as a target. Since
CD19 is expressed at various stages of differentiation of B lymphocytes, and other
non-B cells do not have CD19 expression, CAR targeting CD19 is currently the most
studied CART cell in clinical practice. It has been extensively clinically tested in the
treatment of malignant B-lymphocyte tumors such as B-cell acute lymphoblastic
leukemia (ALL), chronic lymphocytic leukemia (CLL), and non-Hodgkin's
lymphoma. In addition, animal experiments have confirmed that CART cells targeting
CD19 can effectively attack CD19+-expressing B-lymphocyte tumors. In the presence
of immune-deficient mice, CD19+-targeting T cells were found to be effectively
cleared of CD19+ tumor cells.
The study of CD19-CART cells is currently a hot spot for B-cell lymphomas. In 2010,
Kochenderfer et al. first reported the effect of CD19-CART cells in the treatment of
relapsed and refractory follicular lymphoma. In 2012, Kochenderfer et al. reported
that 8 patients with relapsed and refractory B-cell lymphoma received CART cell
therapy, including 4 CLL, 3 follicular neoplasms, and 1 splenic marginal B-cell
lymphoma. The results showed that 1 patient in 8 patients achieved complete
remission (CR), 5 patients achieved partial remission (PR), and 1 patient had stable
disease. The patient's cytokine IFN-γ and TNF levels were detected and 4 of them
were significantly elevated. In 2013 Kochenderfer reported 14 cases of relapsed and
refractory patients, including 8 cases of primary mediastinal large cell lymphoma
(PMBCL) or diffuse large B cell lymphoma (DLBCL), 4 cases of CLL, 1 case of
indolent NHL, 1 case of marginal District B-cell lymphoma (SMZL); 8 cases of
PMBCL or DLBCL were treated with CR or PR after treatment. In 2014, the
Rosenberg team again increased their sample of studies. Twenty-five patients with
refractory and relapsed B lymphocyte tumors were treated with CAR T. Among them,
9 were DLBCL, 4 were CLL, and 2 were indolent lymphoma. The result was 8 cases
of CR. 4 patients achieved PR and 1 patient had stable lymphoma.
The National Cancer Center of the United States also achieved many results in the
treatment of CD19 CAR T cells. They used retrovirus-transfected 19-28 ZCART to
treat B-lymphocyte tumors. Twenty-two of the 27 patients were eligible for CR or PR,
and 1 patient had CR for 37 months. At the 56th ASH meeting in 2014, the center
reported the latest progress: CART treated 9 cases of refractory DLBCL, and
combined with reduced dose chemotherapy, resulted in 1 case of CR, 4 cases of PR,
and 2 cases of poor prognosis.
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, CAR T 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
As a global company, Creative Biolabs has more than 200 talented and well-trained
scientists located in different continents working closely with partners from the entire
world to develop and produce medicines of tomorrow. Specifically, we are the
established leading expert in TCR and CAR T&NK cell immune therapy
development, as we offer the one-stop custom services that cover the entire T cell
development pipeline. Additionally, we also offer an exclusive line of ready-to-use
TCR T cells and CAR T&NK cell construction products, such as virus packaging,
purification, expansion and titer determination kits. Furthermore, we have built up a
unique unparalleled CAR construction and production platform for all four CAR
generations.