ABSTRACT
Engineering a patient's own T cells to accurately identify and eliminate cancer cells has effectively cured individuals afflicted with previously incurable hematologic cancers. These findings have stimulated research into employing chimeric antigen receptor (CAR) T therapy across various areas within the field of oncology. However, evidence from both clinical and preclinical investigations emphasize the broader potential of CAR T therapy, extending beyond oncology to address autoimmune disorders, persistent infections, cardiac fibrosis, age-related ailments and other conditions. Concurrently, the advent of novel technologies and platforms presents additional avenues for utilizing CAR T therapy in non-cancerous contexts. This review provides an overview of the rationale behind CAR T therapy, delineates ongoing challenges in its application to cancer treatment, summarizes recent findings in non-cancerous diseases, and engages in discourse regarding emerging technologies that bear relevance. The review delves into prospective applications of this therapeutic approach across a diverse range of scenarios. Lastly, the review underscores concerns related to precision and safety, while also outlining the envisioned trajectory for extending CAR T therapy beyond cancer treatment.
Subject(s)
Hematologic Neoplasms , Neoplasms , Receptors, Chimeric Antigen , Humans , Receptors, Chimeric Antigen/therapeutic use , Neoplasms/therapy , Immunotherapy, Adoptive , T-Lymphocytes , Hematologic Neoplasms/therapyABSTRACT
Background: Genetic association studies have elucidated the link of variants in the interleukin 17 (IL-17) family genes with susceptibility to human diseases, yet have obtained controversial outcomes. Therefore, we sought to update comprehensive synopsis of variants in the IL-17 family genes with susceptibility to human diseases. Methods: Our study screened the Pubmed and Web of Science to enroll eligible articles and performed a meta-analysis, then graded the cumulative evidence of significant association using Venice criteria and false-positive report probability test, and finally assessed the function of variants with strong evidence. Results: Seven variants in IL-17 family genes had significant relationships with susceptibility to 18 human diseases identified by meta-analyses. Strong evidence was assigned to 4 variants (IL-17A rs2275913, IL-17A rs8193037, IL-17F rs1889570, IL-17F rs763780) with susceptibility to 6 human diseases (lung and cervical cancer, spondyloarthritis, asthma, multiple sclerosis, rheumatoid arthritis), moderate to 2 variants with risk of 5 diseases, weak to 5 variants with risk of 10 diseases. Bioinformatics analysis suggested that the variants with strong evidence might fall in putative functional regions. Additionally, positive relationships for 5 variants with risk of 4 diseases (based on two datasets) and 14 variants with risk of 21 diseases (based on one dataset) were considered noteworthy. Conclusions: This study offers updated and comprehensive clues that variants in the IL-17 family genes are significantly linked with susceptibility to cervical, lung cancer, asthma, multiple sclerosis, rheumatoid arthritis and spondyloarthritis, and elucidates the crucial role of the IL-17 regions in the genetic predisposition to cancer or noncancerous diseases.
Subject(s)
Arthritis, Rheumatoid , Asthma , Lung Neoplasms , Multiple Sclerosis , Spondylarthritis , Humans , Interleukin-17/genetics , Polymorphism, Single Nucleotide , Arthritis, Rheumatoid/genetics , Multiple Sclerosis/genetics , Asthma/geneticsABSTRACT
Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer treatment modality based on a target-specific photosensitizer conjugate (TSPC) composed of an NIR phthalocyanine photosensitizer and an antigen-specific recognition system. NIR-PIT has predominantly been used for targeted therapy of tumors via local irradiation with NIR light, following binding of TSPC to antigen-expressing cells. Physical stress-induced membrane damage is thought to be a major mechanism underlying NIR-PIT-triggered photokilling. Notably, NIR-PIT can rapidly induce immunogenic cell death and activate the adaptive immune response, thereby enabling its combination with immune checkpoint inhibitors. Furthermore, NIR-PIT-triggered "super-enhanced permeability and retention" effects can enhance drug delivery into tumors. Supported by its potential efficacy and safety, NIR-PIT is a rapidly developing therapeutic option for various cancers. Hence, this review seeks to provide an update on the (i) broad range of target molecules suitable for NIR-PIT, (ii) various types of receptor-selective ligands for designing the TSPC "magic bullet," (iii) NIR light parameters, and (iv) strategies for enhancing the efficacy of NIR-PIT. Moreover, we review the potential application of NIR-PIT, including the specific design and efficacy in 19 different cancer types, and its clinical studies. Finally, we summarize possible NIR-PIT applications in noncancerous conditions, including infection, pain, itching, metabolic disease, autoimmune disease, and tissue engineering.
Subject(s)
Neoplasms , Photosensitizing Agents , Photosensitizing Agents/therapeutic use , Photosensitizing Agents/chemistry , Immune Checkpoint Inhibitors , Ligands , Cell Line, Tumor , Immunotherapy , Phototherapy , Xenograft Model Antitumor Assays , Neoplasms/therapyABSTRACT
Objective To investigate the late effect of radiation on child-bearing women,through observing "Fang",a 19-week-pregnant woman at age of 23,who was exposed to 60Co radiation in Shanxi Xinzhou radiation accident in November,1992 and diagnosed as moderate bone marrow type acute radiation sickness and recovered after 16 year of follow-up treatment.Methods Clinical data including medical history,physical examination,laboratory data,imaging findings and consulting relevant departments were reviewed.Results The followed-up woman "Fang" often felt weak and caught cold after recovery.When she was 32 years old (9 years after radiation),her hair turned grey,but without hair loss.Her menstrual quantity was lessened since 31 years old (8 years after radiation).She was remarried and pregnant twice in the same year.At the first time she underwent artificial abortion and the second child suffered from intrauterine death after 6 months of pregnancy.The physical examination found bilateral degree Ⅰ thyroid enlargement and sparse armpit hair.The laboratory test showed the increased levels of triiodothyronine,thyroxine and anti-thyroid peroxidase antibody (TMAb) and the decreased thyroid stimulating hormone (TSH).Unstable chromosome aberrations were totally lost and stable aberrations in chromosomes were detected by fluorescence in situ hybridization (FISH).The dose estimated with the residue chromosome aberration was 0.76 Gy.Other laboratory results were normal.Ultrasonic test showed diffuse lesion in bilateral thyroid and multiple cystic nodules in right lobe of thyroid,which was considered to be nodular goiter.The examination of bone mineral density (BMD) showed osteoporosis from the second to the fourth lumber vertebra.There were no diseases associated with radiation based on the consultation from related departments.Conclusions Intrauterine death after 6 months of pregnancy might be associated with the previous exposure.There is no evidence of malignant tumor,but non-cancerous diseases are obvious.