Development of therapeutics for cancer treatment

描述(申请人提供)：这个项目的目标是开发前列腺癌的新疗法。我们建议开发对靶肿瘤细胞具有高度特异性的新的基于抗体的疗法。肿瘤选择性抗体方法可适用于多种抗体和肿瘤类型。由于肿瘤选择性递送的困难，用抗体治疗许多实体肿瘤是具有挑战性的。单抗特异结合的蛋白质通常在癌细胞表面过度表达，但在某种程度上也在正常细胞上表达。这种表达模式造成了抗体传递的困难，并降低了治疗的特异性。一些抗体的治疗效果也因毒性而受到限制。需要更多的抗体才能达到预期的效果，并导致副作用增加和治疗成本增加。为了提高治疗效果，必须在不引起副作用的情况下增加肿瘤部位抗体的局部浓度。建议的基于抗体的产品在肿瘤部位被激活，其浓度可以达到具有预期治疗效果的水平，而不会出现全身毒性。临床上迫切需要提高抗癌抗体的疗效，以达到理想的治愈率。在第一阶段，我们将开发建议的试剂并进行体外测试。在第二阶段，我们将在评估动物肿瘤治疗的临床前研究中测试这些试剂。

DESCRIPTION (provided by applicant): The goal of this project is to develop novel therapy for prostate cancer. We propose to develop novel antibody-based therapeutics with high specificity for a target tumor cell. The tumor-selective antibody approach can be adapted for many antibodies and tumor types. Treatment of many solid tumors with antibodies is challenging due to difficulties with tumor-selective delivery. Proteins, to which monoclonal antibodies specifically bind, are usually over expressed on surface of cancer cells but also expressed, to some degree, on normal cells. Such expression pattern creates difficulties in the antibody delivery and decreases specificity of the therapy. The therapeutic efficacy of some antibodies is also limited due to toxicity. Higher amounts of antibodies are required to achieve the desired effects and result in increased side effects and higher cost of treatment. To improve the therapeutic efficacy, the local concentration of an antibody in a tumor site has to be increased without causing side effects. The proposed antibody-based product is activated in the tumor site and its concentration can reach levels that have desired therapeutic effects without systemic toxicity. There is urgent clinical need to enhance the efficacy of anticancer antibodies to achieve desirable cure rates for the disease. In Phase I, we will develop proposed reagents and test them invitro. In Phase II, we will test the reagents in preclinical studies evaluating treatment of tumors in animals.