The most dramatic results have been seen with T cells engineered to express a chimeric antigen receptor (CAR) specific for CD19, a differentiation antigen expressed in B cells and B lineage malignancies.
Following the landmark approvals by the United States Food and Drug Administration, the adoptive transfer of CD19-directed chimeric antigen receptor (CAR) T-cells has now entered mainstream clinical practice for patients with chemotherapy-resistant or refractory B-cell malignancies.
It remains challenging to characterize the functional attributes of chimeric antigen receptor (CAR)-engineered T cell product targeting CD19 related to potency and immunotoxicity ex vivo, despite promising in vivo efficacy in patients with B cell malignancies.
Adoptive transfer of T lymphocytes expressing a CD19-specific chimeric antigen receptor (CAR.CD19) induces complete tumor regression in patients with lymphoid malignancies.
Lymphocyte collection at our center was well tolerated and 100% successful in manufacturing CD19-directed CAR T cells from adult patients with B-cell malignancies despite low CE in some patients.
The advent of CD19-targeted CARs for treating patients with multiple forms of advanced B-cell malignancies met with great success, with up to 95% response rates.
MGD011, A CD19 x CD3 Dual-Affinity Retargeting Bi-specific Molecule Incorporating Extended Circulating Half-life for the Treatment of B-Cell Malignancies.
Reviewing the lessons learned thus far in CD19 CAR-T cell trials and how some of these challenges may be overcome will help guide the development of CAR-T cell therapy for malignancies of B-cell origin, as well as for other hematopoietic and non-hematopoietic cancers.
Chimeric antigen receptor (CAR)-engineered T cells (CAR-T cells) have been shown to have unprecedented efficacy in B cell malignancies, most notably in B cell acute lymphoblastic leukemia (B-ALL) with up to a 90% complete remission rate using anti-CD19 CAR-T cells.
Such impressive results with CART19 fostered efforts to expand this technology to other incurable malignancies that naturally do not express CD19, such as acute myeloid leukemia (AML), Hodgkin lymphoma (HL) and multiple myeloma (MM).
Chimeric antigen receptors against CD19 (anti-CD19-CAR) are widely recognized and used by not only researchers associated with immunology, molecular biology, and cell biology but also physicians to treat B-cell malignancies.
ACT based on the administration of cytotoxic T cells genetically engineered to express a chimeric antigen receptor (CAR) recognizing CD19 expressed by B cell malignancies has been shown to induce complete lasting responses in patients with chronic lymphocytic leukaemia (CLL) and acute lymphoblastic leukaemia (ALL).
Tumor regression has been observed following transfer of T cells engineered to express chimeric antigen receptors against CD19 in B-cell malignancies or a T-cell receptor against NY-ESO-1 in synovial cell sarcoma and melanoma.
Adoptive transfer of T cells genetically modified to express chimeric antigen receptors (CARs) targeting CD19 has produced impressive results in treating patients with B-cell malignancies.
T cells expressing CD19-specific chimeric antigen receptors (CARs) with endodomains that encode a signaling domain derived from CD3ζ and CD28 or 41BB have potent antitumor activity in early-phase clinical studies for B-cell malignancies.
Anti-CD19 chimeric antigen receptor (CAR) T cells have caused remissions of B cell malignancies, but problems including cytokine-mediated toxicity and short persistence of CAR T cells in vivo might limit the effectiveness of anti-CD19 CAR T cells.
T cells engineered to express CD19-specific chimeric antigen receptors (CARs) have shown breakthrough clinical successes in patients with B-cell lymphoid malignancies.
The active substance of Kymriah is tisagenlecleucel, an autologous, immunocellular cancer therapy that involves reprogramming the patient's own T cells to identify and eliminate CD19-expressing cells.
Recent early-phase clinical trials of CAR-modified T (CAR-T) cells for relapsed or refractory B cell malignancies have demonstrated promising results (that is, anti-CD19 CAR-T in B cell acute lymphoblastic leukemia (B-ALL)).