The Production of More Effective Monoclonal Antibodies

描述（由申请人提供）：我们建议利用我们最近的发现，在杂交瘤中强制表达AID激活体细胞V区突变，以产生更有效的单克隆抗体，用于生物恐怖主义。我们将测试高速率的V区突变和同型转换，这些可以通过AID的条件表达在体内激活。我们将建立多轮突变和选择的最佳条件，以获得具有全谱同型的最高亲和力的抗体。我们将调整我们以前使用的技术，我们将开发新的技术，使我们能够识别杂交瘤亚克隆，这些杂交瘤亚克隆可以制造人类和小鼠的单克隆抗体，这些抗体将更有效地中和毒素和病毒，并保护我们免受微生物制剂的侵害，这些微生物制剂是生物恐怖主义和细菌战中使用的主要制剂。我们将用小鼠模型来确定这种针对蓖麻毒素和其他毒素的第二代单克隆抗体是否真的更有效。

DESCRIPTION (provided by applicant): We propose to use our recent discovery that the forced expression of AID in hybridomas activates the somatic V region mutation to generate more effective monoclonal antibodies to agents used in bioterrorism. We will test high rates of V region mutation and isotype switching that can be activated in vivo with the conditional expression of AID. We will establish the optimum conditions for multiple rounds of mutation and selection to obtain the highest affinity antibodies with the full spectrum of isotypes. We will adapt techniques that we have used previously and we will develop new ones that will allow us to identify hybridoma subclones that are making human and mouse monoclonal antibodies that will more effectively neutralize the toxins and viruses and protect against microbial agents that are the primary agents used in bioterrorism and germ warfare. We will determine if such second-generation monoclonal antibodies to ricin and other toxins are truly more effective using mouse models.