Suicide gene therapy of rhabdomyosarcoma

Abstract

Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood and young adulthood. Conventional treatment consisting of surgery, chemotherapy and radiotherapy can be insufficient, as long-term survival chances decrease dramatically when cancer recurrence occurs. Due to this fact, efficient treatment of this cancer is still a demanding issue, thus, novel and innovative therapies have to be considered as a part of combined treatment. In the present study, we present effective suicide gene therapy of rhabdomyosarcoma cell line Rh30 involving herpes simplex thymidine kinase (HSV-TK) and ganciclovir (GCV). Transduction of rhabdomyosarcoma cells using lentiviral vectors allowed efficient introduction of HSV-TK gene. In this study we proved high susceptibility of modified cells to ganciclovir resulting in eradication of cancer cells both in vitro and in vivo. Our data revealed strong gap junctional intercellular communication in examined cell line responsible for elimination of unmodified cells by bystander effect, even if HSV-TK-expressing cells comprise only 20% of cultured cells. Moreover, investigated approach is also efficient in vivo, where complete remission of tumors upon only 14 days of systemic administration of GCV can be observed. Obtained results suggest that HSV-TK suicide gene therapy is very promising concept in future clinical studies concerning rhabdomyosarcoma.

Rhabdomyosarcoma, Spindle Cell/Sclerosing Variant: A Clinical and Histopathological Examination of this Rare Variant with Three New Cases from the Oral Cavity

“…Most RMS are treated with conventional surgery, chemotherapy, and radiotherapy. Chemotherapeutic agents typically consist of actinomycin D, doxorubicin, ifosfamide, cyclophosphamide, etoposide, or vincristine [19]. Despite efforts at various treatment techniques, the prognosis for RMS, especially S-ScRMS, remains poor [4,9], and longterm survival decreases significantly when the patient exhibits recurrence [19].…”

“…Chemotherapeutic agents typically consist of actinomycin D, doxorubicin, ifosfamide, cyclophosphamide, etoposide, or vincristine [19]. Despite efforts at various treatment techniques, the prognosis for RMS, especially S-ScRMS, remains poor [4,9], and longterm survival decreases significantly when the patient exhibits recurrence [19]. When patients do survive, longterm sequela from treatment, including facial asymmetry, tooth formation abnormalities, jaw hypoplasia, trismus, and hyposalivation/xerostomia may remain and significantly alter patient's lifestyles [20].…”

“…When patients do survive, longterm sequela from treatment, including facial asymmetry, tooth formation abnormalities, jaw hypoplasia, trismus, and hyposalivation/xerostomia may remain and significantly alter patient's lifestyles [20]. Recent research into immunotherapy using monoclonal antibodies or suicide gene therapy seems promising [19].…”

Engineering and Characterization of Oncolytic Vaccinia Virus Expressing Truncated Herpes Simplex Virus Thymidine Kinase

“…The virus dosages used in this study (10 6 PFU for IT and 10 8 PFU for IP) were based on our previous studies on other OVVs [11,12]. The GCV dosages that were used in this study (25 and 50 mg/kg/day) were commonly adopted by many other animal studies [44,45] and, according to a widely used human-animal drug dose translation equation [46], mouse dose of 50 mg/kg/day is equivalent to the recommended maintenance dosages for humans, which is around 5 mg/kg/day.…”

Terapia génica en el arsenal de terapéutica de la enfermedad oncológica.

“…Aunque es necesario investigar más sobre el efecto de la exposición prolongada a GcV y la eficiencia de la eliminación tumoral con un bajo porcentaje de células HSV-TK presentes en el tumor para establecer la seguridad y la eficiencia de dicho tratamiento, la terapia génica suicida es un concepto muy prometedor. futuros estudios clínicos sobre el rabdomiosarcoma (25).…”