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.

腹膜癌是美国的主要健康问题。有超过 230,000 例新发癌症病例来自腹膜腔器官。制药公司通常专注于静脉或口服给药的药物。然而，由于肿瘤中血液灌注不足和组织间液压力高，全身治疗通常无法向实体瘤提供足够的药物水平。另一方面，腹膜内 (ip) 化疗在多项 NIH 资助的随机试验中显示出令人印象深刻的生存优势。由于缺乏经批准的腹腔注射产品，这些早期研究使用了静脉注射制剂。这种方法有两个局限性：(a) 限制药物渗透到肿瘤周围，降低了肿瘤较大 (>1 cm) 患者的腹膜内治疗的疗效，b) 腹膜内治疗与感染（由于留置导管）和毒性有关局部药物浓度高（腹痛）。尽管腹膜内治疗已被证明有效，但这些问题阻碍了腹膜内治疗的广泛使用。