Background: Osteosarcoma (OS) mainly happens in children and youths. Surgery, radiotherapy and chemotherapy are the common therapies for osteosarcoma treatment but all their anti-tumor effects are limited. In recent years, a new cellular therapy, CAR-T, a cellular immunotherapy with genetically engineered T cells bearing chimeric antigen receptor targeting specific tumor-associated antigen, has been proved to be an effective therapy against acute lymphoblastic leukemia. Thus, CAR-T is a potentially effective therapy for osteosarcoma treatment.
Methods: A CAR gene targeting B7-H3 antigen was constructed into lentiviral vector through molecular biology techniques. Then, the CAR gene was transferred to T cells through lentiviral delivery system, and the CAR-T cells were largely expanded using in vitro culture technology. The in vitro anti-tumor effect of CAR-T cells was evaluated through Real Time Cell Analysis system (RTCA) and ELISA assay. The in vivo anti-tumor capabilities of CAR-T cells were evaluated using the patient-derived xenografts (PDX) model of osteosarcoma.
Results: The third-generation CAR-T cells we constructed could target the B7-H3 antigen, and the phenotype of CAR-T cells was consistent with normal T cells; The CAR-T cells showed superior antitumor effects both in vitro and in vivo.
Conclusion: Our study showed that B7-H3 targeted CAR-T cells had high anti-tumor efficacy against osteosarcoma both in vitro and in vivo, which proved that B7-H3 targeted CAR-T therapy is potentially effective for osteosarcoma treatment.
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http://dx.doi.org/10.1186/s12885-022-10229-8 | DOI Listing |
Here we report results of a phase 1 multi-institutional, open-label, dose-escalation trial (NCT02744287) of BPX-601, an investigational autologous PSCA-directed GoCAR-T® cell product containing an inducible MyD88/CD40 ON-switch responsive to the activating dimerizer rimiducid, in patients with metastatic pancreatic (mPDAC) or castration-resistant prostate cancer (mCRPC). Primary objectives were to evaluate safety and tolerability and determine the recommended phase 2 dose/schedule (RP2D). Secondary objectives included the assessment of efficacy and characterization of the pharmacokinetics of rimiducid.
View Article and Find Full Text PDFFront Immunol
December 2024
Myeloid Therapeutics, Inc., Cambridge, MA, United States.
Introduction: The approval of chimeric antigen receptor (CAR) T cell therapies for the treatment of B cell malignancies has fueled the development of numerous cell therapies. However, these cell therapies are complex and costly, and unlike in hematological malignancies, outcomes with most T cell therapies in solid tumors have been disappointing. Here, we present a novel approach to directly program myeloid cells by administering novel TROP2 CAR mRNA encapsulated in lipid nanoparticles (LNPs).
View Article and Find Full Text PDFBME Front
December 2024
Department of Aerospace and Mechanical Engineering, University of Southern California, Los Angeles, CA 90089, USA.
Deep-tissue solid cancer treatment has a poor prognosis, resulting in a very low 5-year patient survival rate. The primary challenges facing solid tumor therapies are accessibility, incomplete surgical removal of tumor tissue, the resistance of the hypoxic and heterogeneous tumor microenvironment to chemotherapy and radiation, and suffering caused by off-target toxicities. Here, sonodynamic therapy (SDT) is an evolving therapeutic approach that uses low-intensity ultrasound to target deep-tissue solid tumors.
View Article and Find Full Text PDFTher Adv Med Oncol
December 2024
Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, Zhejiang Province 310003, China.
Chimeric antigen receptor T (CAR T) cells have shown their potential in hematological malignancies and the treatment of solid tumors, especially in metastases. However, CAR T-cell therapy may carry risks of inducing severe adverse effects, which are recognized as immune-related adverse events. Here, we report two cases of severe colitis presented with refractory bloody diarrhea, which were induced by carcinoembryonic antigen (CEA)-directed CAR T therapy in the treatment of metastatic colorectal adenocarcinoma.
View Article and Find Full Text PDFCurr Opin Endocr Metab Res
December 2024
Human thyroid cancers preclinical and translational research program, Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Thyroid cancer treatment has recently been revolutionized by the introduction of specific targeted therapies (e.g. BRAF or highly selective RET inhibitors), anti-angiogenic agents (e.
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