The application of CAR-T cell therapy in hematological malignancies: advantages and challenges

Abstract

Chimeric antigen receptor T cell (CAR-T cell) therapy is a novel adoptive immunotherapy where T lymphocytes are engineered with synthetic receptors known as chimeric antigen receptors (CAR). The CAR-T cell is an effector T cell that recognizes and eliminates specific cancer cells, independent of major histocompatibility complex molecules. The whole procedure of CAR-T cell production is not well understood. The CAR-T cell has been used predominantly in the treatment of hematological malignancies, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, lymphoma, and multiple myeloma. Solid tumors including melanoma, breast cancer and sarcoma offer great promise in CAR-T cell research and development. CD19 CAR-T cell is most commonly used, and other targets, including CD20, CD30, CD38 and CD138 are being studied. Although this novel therapy is promising, there are several disadvantages. In this review we discuss the applications of CAR-T cells in different hematological malignancies, and pave a way for future improvement on the effectiveness and persistence of these adoptive cell therapies.

The Role of Checkpoint Inhibitors and Cytokines in Adoptive Cell-Based Cancer Immunotherapy with Genetically Modified T Cells

“…Indeed, clinical trials of the last few years have demonstrated a high effi cacy of CAR T therapy in the treatment of refractory B cell neoplasms. Large scale clinical trials, which have granted approval for the two products based on CD19 specific CAR T, demonstrated sustained efficacy of these products in the treatment of malignant B cell neoplasms (B ALL, non Hodgkin lymphoma) resulting in a com plete recovery in 70 90% patients with relapsed B ALL [28,29].…”

CAR-T Cell Therapy in Cancer: Tribulations and Road Ahead

“…The CD19 CAR-T cells of the clinical trial are summarized in Table 2. Clinical studies at several different institutions have used CD19 CAR-T cell therapy in children and adults with recurrent B cell acute lymphoblastic leukemia (B-ALL), B cell non-Hodgkin's lymphoma (B-NHL), and chronic lymphocytic leukemia (CLL), and these studies showed high antitumor treatment efficacy [77,78]. As of August 2017, there were approximately 200 clinical trials involving CAR-T cells worldwide [79].…”

Chimeric Antigen Receptor-T-Cell Therapy

“…Antijen tanıyan bölge, tümör ilişkili antijene karşı tipik bir tek zincirli değişken fragman (scFv) antikorudur. 2 T-hücre sinyal domaini ise, T-hücre aktivasyon domaini (CD3zeta) ve ko-stimülatör domainden (CD28, CD134 (OX40) veya CD137 (4-1BB) gibi) oluşmaktadır. Reseptörün aralayıcı (hinge/spacer) ve transmembran bölgeleri ise ekstraselüler antijen tanıyan domaini, sitoplazmik sinyalizasyon domainine bağlamaktadır (Şekil 1).…”

“…İnfüze edilen CAR-T-hücreler dolaşımda medyan 30-300 gün kalırlar. 2,[6][7][8][9][10] CAR-T HÜCRE TEDAVİSİNİN YAN ETKİLERİ…”