T cell malignancies represent a group of hematologic cancers with high rates of relapse and mortality in patients for whom no effective targeted therapies exist. The shared expression of target antigens between chimeric antigen receptor (CAR) T cells and malignant T cells has limited the development of CAR-T because of unintended CAR-T fratricide and an inability to harvest sufficient autologous T cells. Here we describe a fratricide resistant ‘off-the-shelf’ CAR-T (or UCART7) that targets CD7+ T cell malignancies and, through CRISPR/Cas9 gene editing, lacks both CD7 and T cell receptor alpha chain (TRAC) expression. UCART7 demonstrates efficacy against human T cell acute lymphoblastic leukemia (T-ALL) cell lines and primary T-ALL in vitro and in vivo without the induction of xenogeneic GvHD. Fratricide resistant, allo-tolerant ‘off-the-shelf’ CAR-T represents a strategy for treatment of relapsed and refractory T-ALL and non-Hodgkin’s T cell lymphoma without a requirement for autologous T cells.

Space travel has advanced significantly over the last six decades with astronauts spending up to 6 months at the International Space Station. Nonetheless, the living environment while in outer space is extremely challenging to astronauts. In particular, exposure to space radiation represents a serious potential long-term threat to the health of astronauts because the amount of radiation exposure accumulates during their time in space. Therefore, health risks associated with exposure to space radiation are an important topic in space travel, and characterizing space radiation in detail is essential for improving the safety of space missions. In the first part of this review, we provide an overview of the space radiation environment and briefly present current and future endeavors that monitor different space radiation environments. We then present research evaluating adverse biological effects caused by exposure to various space radiation environments and how these can be reduced. We especially consider the deleterious effects on cellular DNA and how cells activate DNA repair mechanisms. The latest technologies being developed, e.g., a fluorescent ubiquitination-based cell cycle indicator, to measure real-time cell cycle progression and DNA damage caused by exposure to ultraviolet radiation are presented. Progress in examining the combined effects of microgravity and radiation to animals and plants are summarized, and our current understanding of the relationship between psychological stress and radiation is presented. Finally, we provide details about protective agents and the study of organisms that are highly resistant to radiation and how their biological mechanisms may aid developing novel technologies that alleviate biological damage caused by radiation. Future research that furthers our understanding of the effects of space radiation on human health will facilitate risk-mitigating strategies to enable long-term space and planetary exploration.

3.

During a space mission, astronauts are inevitably exposed to space radiation, mainly composed of the particles having high values of linear energy transfer (LET), such as protons, helium nuclei, and other heavier ions. Those high-LET particles could induce severer health damages than low-LET particles such as photons and electrons. While it is known that the biological effectiveness of a specified type of radiation depends on the distribution of dose in time, type of the cell, and the biological endpoint in respect, there are still large uncertainties regarding the effects of high-LET particles on the reproductive system, gamete, embryo, and fetal development because of the limitation of relevant data from epidemiological and experimental studies. To safely achieve the planned deep space missions to the moon and Mars that would involve young astronauts having reproductive functions, it is crucial to know exactly the relevant radiological effects, such as infertility of the parent and various diseases of the child, and then to conduct proper countermeasures. Thus, in this review, the authors present currently available information regarding the relative biological effectiveness (RBE) of high-LET particles on the deterministic effects related to the reproductive system and embryonic/fetal development for further discussions about the safety of being pregnant after or during a long-term interplanetary mission.

Radiotherapy remains currently a critical component for both primary and metastatic brain tumors either alone or in combination with surgery, chemotherapy, and molecularly targeted agents, while it could cause simultaneously normal brain tissue injury leading to serious health consequences, that is, development of cognitive impairments following cranial radiotherapy is considered as a critical clinical disadvantage especially for the whole brain radiotherapy. Biomarkers can help to detect the accurate physiology or conditions of patients with brain tumor and develop effective treatment procedures for these patients. In the near future, biomarkers will become one of the prime driving forces of cancer treatment. In this minireview, we analyze the documented work on the acute brain damage and late consequences induced by radiotherapy, identify the biomarkers, in particular, the predictive biomarkers for the damage, and summarize the biological significance of the biomarkers. It is expected that translation of these research advance to radiotherapy would assist stratifying patients for optimized treatment and improving therapeutic efficacy and the quality of life.

Radiation damage assessment of the small intestine is important in nuclear accidents or routine radiotherapy of abdominal tumors. This article reviews the clinical symptoms and molecular mechanisms of radiation-induced small intestinal damage and summarizes recent research on biomarkers of such damage. Citrulline is the most promising biomarker for the evaluation of radiation-induced small intestinal damage caused by radiotherapy and nuclear accidents. This article also summarizes the factors influencing plasma citrulline measurement investigated in the latest research, as well as new findings on the concentration of citrulline in saliva and urine after different types of radiation.

Radioadaptive response (RAR) describes a phenomenon in a variety of in vitro and in vivo systems that a low-dose of priming ionizing radiation (IR) reduces detrimental effects of a subsequent challenge IR at higher doses. Among in vivo investigations, studies using the mouse RAR model (Yonezawa Effect) showed that RAR could significantly extenuate high-dose IR-induced detrimental effects such as decrease of hematopoietic stem cells and progenitor cells, acute radiation hematopoietic syndrome, genotoxicity and genomic instability. Meanwhile, it has been demonstrated that diet intervention has a great impact on health, and dietary restriction shows beneficial effects on numerous diseases in animal models. In this work, by using the mouse RAR model and mild dietary restriction (MDR), we confirmed that combination of RAR and MDR could more efficiently reduce radiogenotoxic damage without significant change of the RAR phenotype. These findings suggested that MDR may share some common pathways with RAR to activate mechanisms consequently resulting in suppression of genotoxicity. As MDR could also increase resistance to chemotherapy and radiotherapy in normal cells, we propose that combination of MDR, RAR, and other cancer treatments (i.e., chemotherapy and radiotherapy) represent a potential strategy to increase the treatment efficacy and prevent IR risk in humans.

Gastrointestinal (GI) microbiota maintains a symbiotic relationship with the host and plays a key role in modulating many important biological processes and functions of the host, such as metabolism, inflammation, immune and stress response. It is becoming increasingly apparent that GI microbiota is susceptible to a wide range of environmental factors and insults, for examples, geographic location of birth, diet, use of antibiotics, and exposure to radiation. Alterations in GI microbiota link to various diseases, including radiation-induced disorders. In addition, GI microbiota composition could be used as a biomarker to estimate radiosusceptibility and radiation health risk in the host. In this minireview, we summarized the documented studies on radiation-induced alterations in GI microbiota and the relationship between GI microbiota and radiosusceptibility of the host, and mainly discussed the possible mechanisms underlying GI microbiota influencing the outcome of radiation response in humans and animal models. Furthermore, we proposed that GI microbiota manipulation may be used to reduce radiation injury and improve the health of the host.