ABSTRACT
The engineering of immune cells to target cancer cells (cellular immunotherapy) has been an exciting area of development in recent years. One type of cellular therapy, T cell receptor (TCR) gene engineered therapy, has shown particular promise in solid tumors. Through use of a heterodimer to recognize intracellular tumor antigens presented through the major histocompatibility complex (MHC), TCR T cells are able to evoke a cytotoxic response as well as a clinical response. In this review, we discuss the potential of TCR-based cellular therapies in solid tumors. While various challenges exist with this therapy, multiple clinical trials are ongoing, in attempt to mitigate these limitations.
Subject(s)
Neoplasms , Receptors, Antigen, T-Cell , Antigens, Neoplasm , Cell- and Tissue-Based Therapy , Genes, T-Cell Receptor , Humans , Immunotherapy, Adoptive , Neoplasms/genetics , Neoplasms/therapy , Receptors, Antigen, T-Cell/geneticsABSTRACT
We compared CMV outcomes of three prophylactic approaches used for CBT and haploidentical cord transplants from December 2009 through 2018: letermovir (n = 32) through day 100 post transplant, "valacyclovir day 100" (valacyclovir 2 g orally three times daily through day 100) (n = 60), and "valacyclovir hospital discharge" (valacyclovir 2 g orally three times daily through hospital discharge then acyclovir 800 mg twice daily) (n = 41). Through day 100, none in the letermovir group, six (10%) in the "valacyclovir day 100," and nine (22%) in the "valacyclovir hospital discharge" group required CMV directed treatment (p = 0.005 and 0.06 comparing letermovir to "valacyclovir hospital discharge" and "valacyclovir day 100"). Fewer patients in the letermovir group (n = 7, 22%) had any CMV reactivation versus the "valacyclovir day 100" group (n = 20, 33%) versus the "valacyclovir hospital discharge" group (n = 23, 57%) (p = 0.003 and 0.21 comparing letermovir to "valacyclovir hospital discharge" and "valacyclovir day 100"). Among patients not reactivating CMV before 100 days, reactivation rates between day 100 and 180 were higher in the letermovir and "valacyclovir day 100" groups than the "valacyclovir hospital discharge" group. Letermovir is safe and effective compared with alternative prophylaxis approaches following CBT through day 100. Reactivation and monitoring after day 100 remain potential concerns.
Subject(s)
Cord Blood Stem Cell Transplantation , Cytomegalovirus Infections , Acetates , Adult , Antiviral Agents/therapeutic use , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/prevention & control , Fetal Blood , Humans , QuinazolinesABSTRACT
Vasculitis is an inflammatory condition that targets the blood vessels, which may occur in isolation or as a component of a systemic inflammatory condition. Although many of the vasculitides can directly affect the organs of the gastrointestinal system, some types exhibit a proclivity for certain gastrointestinal and hepatic organs. Often a patient presents with nonspecific symptoms, delaying the diagnosis and treatment of the underlying vasculitis. Vasculitis can also present with severe manifestations, such as upper gastrointestinal bleeds and bowel perforation. It is important to identify the signs and symptoms of vasculitis in gastrointestinal system and institute appropriate treatment.