Retroviral transfer of human CD20 as a suicide gene for adoptive T-cell therapy.
نویسندگان
چکیده
The aim of adoptive T-cell therapy of cancer is to selectively confer immunity against tumor cells. Autoimmune side effects, however, remain a risk, emphasizing the relevance of a suicide mechanism allowing in vivo elimination of infused T cells. We investigated the use of human CD20 as suicide gene in T-lymphocytes. Potential effects of forced CD20 expression on T-cell function were investigated by comparing CD20- and mock-transduced cytomegalovirus (CMV) specific T cells for cytolysis, cytokine release and proliferation. The use of CD20 as suicide gene was investigated in CMV specific T cells and in T cells genetically modified with an antigen specific T-cell receptor. No effect of CD20 on T-cell function was observed. CD20-transduced T cells with and without co-transferred T-cell receptor were efficiently eliminated by complement dependent cytotoxicity induced by therapeutic anti-CD20 antibody rituximab. The data support the broad value of CD20 as safety switch in adoptive T-cell therapy.
منابع مشابه
An Efficient Large-Scale Retroviral Transduction Method Involving Preloading the Vector into a RetroNectin-Coated Bag with Low-Temperature Shaking
In retroviral vector-mediated gene transfer, transduction efficiency can be hampered by inhibitory molecules derived from the culture fluid of virus producer cell lines. To remove these inhibitory molecules to enable better gene transduction, we had previously developed a transduction method using a fibronectin fragment-coated vessel (i.e., the RetroNectin-bound virus transduction method). In t...
متن کاملConstruction and cloning of a recombinant expression vector containing human Cd20 Gene for antibody therapy in Non-Hodgkin Lymphoma
ABSTRACT Introduction: Non-Hodgkin lymphoma (NHL) is a cancer that starts in lymphocytes. The main treatment for NHL is chemotherapy and radiation. Today immunotherapy is a promising therapeutic approach in the treatment of a variety cancers which is high specific unlike previous methods. Antibodies do not penetrate effectively into tumore tissues because of their large size. Whe...
متن کاملP71. Adoptive transfer of TCR gene-transduced lymphocytes targeting MAGE-A4 for refractory esophageal cancer
Materials and methods MAGE-A4-specific TCR a and b chains were cloned from a human T cell clone that recognises MAGEA4143-151 peptide in a HLA-A*24:02 restricted manner. This T cell clone did not show any cross reactivity to the peptides with homology to the MAGE-A4143-151 epitope. A retroviral vector that encodes these TCR chains without any artificial modification was constructed; the lymphoc...
متن کاملAn Enterovirus-Like RNA Construct for Colon Cancer Suicide Gene Therapy
Background: In gene therapy, the use of RNA molecules as therapeutic agents has shown advantages over plasmid DNA, including higher levels of safety. However, transient nature of RNA has been a major obstacle in application of RNA in gene therapy. Methods: Here, we used the internal ribosomal entry site of encephalomyocarditis virus and the 3’ non-translated region of Poliovirus to design an en...
متن کاملThe Effect of Herpes Simplex Virus Virion Host Shutoff Gene- a New Suicide Gene- on Tumor Cells
Background: The herpes simplex virus (HSV) UL41 gene product, virion host shutoff (Vhs) protein, mediates the rapid degradation of both viral and cellular mRNA. This ability suggests that Vhs protein can be used as a suicide gene in cancer gene therapy applications. The recent reports have shown that the degradation of cellular mRNA during herpes simplex infection is selective. RNA containing A...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Haematologica
دوره 94 9 شماره
صفحات -
تاریخ انتشار 2009