Finding new lanes: Chimeric antigen receptor (CAR) T-cells for myeloid leukemia.

BACKGROUND: Myeloid leukemia represents a heterogeneous group of cancers of blood and bone marrow which arise from clonal expansion of hematopoietic myeloid lineage cells. Acute myeloid leukemia (AML) has traditionally been treated with multi-agent chemotherapy, but conventional therapies have not improved the long-term survival for decades. Chronic myeloid leukemia (CML) is an indolent disease which requires lifelong treatment, is associated with significant side effects, and carries a risk of progression to potentially lethal blast crises. RECENT FINDINGS: Recent advances in molecular biology, virology, and immunology have enabled researchers to grow and modify T lymphocytes ex-vivo. Chimeric antigen receptor (CAR) T-cell therapy has been shown to specifically target cells of lymphoid lineage and induce remission in acute lymphoblastic leukemia (ALL) patients. While the success of CAR T-cells against ALL is considered a defining moment in modern oncology, similar efficacy against myeloid leukemia cells remains elusive. Over the past 10 years, numerous CAR T-cells have been developed that can target novel myeloid antigens, and many clinical trials are finally starting to yield encouraging results. In this review, we present the recent advances in this field and discuss strategies for future development of myeloid targeting CAR T-cell therapy. CONCLUSIONS: The field of CAR T-cell therapy has rapidly evolved over the past few years. It represents a radically new approach towards cancers, and with continued refinement it may become a viable therapeutic option for patients of acute and chronic myeloid leukemia.

Molecular and cellular genetics of non-Hodgkin lymphoma: Diagnostic and prognostic implications.

Non-Hodgkin lymphoma (NHL) is a diverse collection of malignant neoplasms with lymphoid-cell origin which includes all the malignant lymphomas that are not classified as Hodgkin lymphoma. NHL is one of the most common types of cancer diagnosed in men and women in the developed world. In the United States of America, the past few decades have seen a significant rise in the incidence of NHL and it accounts for about 4% of all cancers now. The overall survival of NHL has improved drastically over the past ten years. This can be attributed to better understanding of pathogenesis, refined classification, enhanced supportive care, and data from collaborative clinical trials. The prognosis of a newly diagnosed NHL patient depends, among other factors, on the specific subtype of lymphoma, stage of the disease, and age of the patient. Advances in the fields of molecular biology and innovations in cytogenetic techniques have led to the discovery of several oncogenic pathways involved in lymphomagenesis, which in turn has amplified the diagnostic and therapeutic approaches available for NHL. Our comprehension of the genetic features that determine the character of NHL, and ultimately guide the therapy, has undergone significant shift and it is essential that scientists as well as clinicians stay in tune with this rapidly evolving knowledge. In this review we have summarized the current concepts about cellular and molecular genetics of the common subtypes of NHL and their clinical implications.

Pre-Clinical Evaluation of rHDL Encapsulated Retinoids for the Treatment of Neuroblastoma.

Despite major advances in pediatric cancer research, there has been only modest progress in the survival of children with high risk neuroblastoma (NB) (HRNB). The long term survival rates of HRNB in the United States are still only 30-50%. Due to resistance that often develops during therapy, development of new effective strategies is essential to improve the survival and overcome the tendency of HRNB patients to relapse subsequent to initial treatment. Current chemotherapy regimens also have a serious limitation due to off target toxicity. In the present work, we evaluated the potential application of reconstituted high density lipoprotein (rHDL) containing fenretinide (FR) nanoparticles as a novel approach to current NB therapeutics. The characterization and stability studies of rHDL-FR nanoparticles showed small size (<40 nm) and high encapsulation efficiency. The cytotoxicity studies of free FR vs. rHDL/FR toward the NB cell lines SK-N-SH and SMS-KCNR showed 2.8- and 2-fold lower IC50 values for the rHDL encapsulated FR vs. free FR. More importantly, the IC50 value for retinal pigment epithelial cells (ARPE-19), a recipient of off target toxicity during FR therapy, was over 40 times higher for the rHDL/FR as compared to that of free FR. The overall improvement in in vitro selective therapeutic efficiency was thus about 100-fold upon encapsulation of the drug into the rHDL nanoparticles. These studies support the potential value of this novel drug delivery platform for treating pediatric cancers in general, and NB in particular.