MANUFACTURING OF TPM SUITABLE FOR HUMAN USE

制造适合人类使用的 TPM

• 批准号: 10941243
• 负责人: max moore
• 金额: $ 154.68万
• 依托单位: LEIDOS BIOMEDICAL RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2028-09-14
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10941243
• 关键词: MANUFACTURING; TPM; SUITABLE; HUMAN; USE

Peritoneal cancers are major health concerns in the US. There are over 230,000 new cases of cancers arising from organs in the peritoneal cavity. Pharmaceutical companies generally focus on drugs given by intravenous or oral administration. However, systemic therapy often does not deliver sufficient drug levels to solid tumors due to inadequate blood perfusion and high interstitial fluid pressure in tumors. On the other hand, intraperitoneal (ip) chemotherapy has demonstrated impressive survival advantage in multiple NIH-funded randomized trials. Due to the lack of approved ip products, these earlier studies had used intravenous formulations. This approach has two limitations: (a) restricted drug penetration to the tumor periphery diminishes the efficacy of ip treatment in patients with larger tumors (>1 cm), and b) ip therapy is associated with infection (due to indwelling catheter) and toxicity from high local drug levels (abdominal pain). These problems have prevented wide-spread use of ip therapy in spite of the demonstrated efficacy.

在美国，腹膜癌是主要的健康问题。有超过23万例新的癌症病例是由腹腔器官引起的。制药公司通常专注于静脉或口服给药。然而，由于肿瘤内血液灌注不足和间质液压力高，全身治疗往往不能给实体瘤提供足够的药物水平。另一方面，在多个nih资助的随机试验中，腹腔化疗显示出令人印象深刻的生存优势。由于缺乏批准的ip产品，这些早期的研究使用静脉注射制剂。这种方法有两个局限性：(a)药物对肿瘤周围的渗透受限，降低了较大肿瘤（bbb1cm）患者的ip治疗效果；(b) ip治疗与感染（由于留置导管）和高局部药物水平的毒性（腹痛）有关。这些问题阻碍了ip疗法的广泛应用，尽管它已被证明有效。