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  • Title: Auto T cells expressing chimeric antigen receptor derived from auto antibody might be a new treatment for osteosarcoma.
    Author: Weibo P, Zhaoming Y.
    Journal: Med Hypotheses; 2012 May; 78(5):616-8. PubMed ID: 22330890.
    Abstract:
    Osteosarcoma is the most common primary malignant tumor of bone. Except for the improvement in five-year survival achieved by the adoption of neoadjuvant chemotherapy strategy, there are nearly no improvement for the treatment of osteosarcoma in the past 30 years, especially for the patients with metastatic disease. Immunotherapy has been successfully applied in some tumors. The survival of osteosarcoma patients enrolled in several clinical immunotherapy trials did be improved in the past. Immunotherapy might further improve the therapy result of osteosarcoma patients besides neoadjuvant chemotherapy. But there still are many problems needed to be solved before clinically successful application. Immune escape is one of the main obstacles hindering the immunotherapy for osteosarcoma. No effective tumor antigens, or in other words, attenuated immunogenicity is one of the main mechanisms of immune escape. So the key point of immunotherapy for osteosarcoma is to find out an effective target through which the immune system can recognize this tumor and attack it. Genetic modification of immune system may circumvent this problem by enhancing the capacity of immune system. Chimeric antigen receptor (CAR), an artificial receptor generated by genetic manipulation, is a promising technique. The CAR technique can circumvent the restriction of major histocompatibility in antigen recognition for T cells, and is more effective than the corresponding antibody to get rid of tumor cells. But short persistence of the CAR expressing T cells in vivo is the main problem of CAR technique in current research. This problem is believed to have some relation to the immunogenicity of the artificial receptor because the antigen recognizing portion of receptor is derived from monoclonal antibody. So we believe that the elimination of the immunogenicity of CAR might prolong the persistence of CAR expressing T cells in vivo and put forward a hypothesis that the antigen binding portion of CAR could be derived from the antibody against osteosarcoma antigen from the same patient with osteosarcoma by methods such as antibody phage display, BRASIL technique. We believe that CAR expressing T cells constructed by this strategy would persist longer and are more effective to eradicate osteosarcoma cells. In addition, this treatment strategy is an individualized treatment because an effective target specific to the CAR could be found. Therefore the immune escape of osteosarcoma would be surmounted and the survival of patients would be improved.
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