Uses of IL-12 as a Hematological Adjuvant Cancer Therapy

IL-12 作为血液辅助癌症治疗的用途

• 批准号: 6831072
• 负责人: DAN DOUER
• 金额: $ 30万
• 依托单位: NEUMEDICINES, LLC
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-17 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6831072
• 关键词: combination cancer therapy; hematology; immunomodulators; interleukin 12; laboratory mouse; neoplasm /cancer chemotherapy; neoplasm /cancer immunotherapy; neoplasm /cancer radiation therapy; oncology; therapy design /development; whole body imaging /scanning

DESCRIPTION (provided by applicant): The long term and overall goal of the proposed Phase I and Phase II studies is to develop the commercial use of Interleukin-12 (IL-12) as a hematological adjuvant cancer therapy to radiation therapy, chemotherapy and combined approaches. This goal, if attained, should yield greater success in treating various cancers by reducing the hematologic toxicity of currently practiced cancer treatment modalities. Moreover, the development of IL-12 for hematopoietic recovery could obviate the need for hematopoietic transplants, i.e, bone marrow or stem cell transplants, as currently practiced in the fields of oncology and hematology. More specifically, the proposed Phase I studies are aimed at assessing the feasibility of using IL-12 as a countervailing treatment, i.e., as a hematological adjuvant therapy, to alleviate the hematological toxicity associated with various cancer treatment modalities. Moreover, since IL-12 is known to possess significant anti-tumorgenic and anti-angiogenic properties, the use of IL-12 for enhancing hematopoietic recovery may concomitantly yield overall higher cancer remission and survival rates. The applicant, Neumedicines, LLC, in collaboration with scientists from the University of Southern California (USC), has discovered that IL-12 is uniquely effective is rescuing subjects from the effects of total body lethal irradiation (TBI). Merely one, low dose of IL-12 alone (without the use of any added blood cells) administered either shortly before or immediately after total body irradiation results in near complete survival rates. Moreover, no ostensible toxicity is observed following IL-12 treatment, Thus, we propose 1) that IL-12 can be developed as a hematological adjuvant therapy to radiation and chemotherapy using mouse model systems (Phase I), and 2) that this adjuvant use of IL-12 may provide a means of obviating or reducing the clinical use of bone marrow or hematopoietic stem cell transplants. Moreover, although the anti-tumor effects of IL-12 are replete in the literature of the past ten years, no clinical approvals of the use of IL- 12 in cancer have been obtained. Given the known anti-tumorgenic, as well as anti-angiogenic, properties of IL-12, we speculate that the hematological adjuvant use of IL-12 with radiation therapy and/or chemotherapy will allow therapeutic regimens to be developed that will concomitantly yield greater tumor remission and survival rates along with improved hematopoietic recovery. The use of IL-12 as a hematological adjuvant therapy to radiation therapy and/or chemotherapy represents a novel application of IL- 12 in cancer biology.

描述（由申请人提供）：拟定I期和II期研究的长期和总体目标是开发白细胞介素-12（IL-12）作为放射治疗、化疗和联合方法的血液学辅助癌症治疗的商业用途。 如果达到这一目标，通过减少目前实践的癌症治疗方式的血液毒性，在治疗各种癌症方面应该会取得更大的成功。 此外，用于造血恢复的IL-12的开发可以减少对造血移植的需要，即骨髓或干细胞移植，如目前在肿瘤学和血液学领域中所实施的。 更具体地说，拟议的I期研究旨在评估使用IL-12作为抵消治疗的可行性，即，作为血液学辅助治疗，以减轻与各种癌症治疗方式相关的血液学毒性。 此外，由于已知IL-12具有显著的抗肿瘤和抗血管生成特性，因此使用IL-12增强造血恢复可伴随产生总体较高的癌症缓解率和存活率。 申请人Neumedicines，LLC与南加州大学（USC）的科学家合作，发现IL-12在挽救受试者免受全身致死辐射（TBI）影响方面具有独特的有效性。 在全身照射之前不久或之后立即施用仅一个低剂量的单独IL-12（不使用任何添加的血细胞）导致接近完全的存活率。 此外，在IL-12治疗后没有观察到明显的毒性。因此，我们提出1）可以使用小鼠模型系统（I期）开发IL-12作为放射和化学疗法的血液学辅助疗法，和2）IL-12的这种辅助使用可以提供避免或减少骨髓或造血干细胞移植的临床使用的手段。 此外，尽管IL-12的抗肿瘤作用在过去十年的文献中是充分的，但尚未获得在癌症中使用IL- 12的临床批准。 考虑到IL-12已知的抗肿瘤性以及抗血管生成性，我们推测IL-12与放射疗法和/或化学疗法的血液学辅助使用将允许开发伴随产生更大的肿瘤缓解率和存活率沿着改善的造血恢复的治疗方案。 IL-12作为放射疗法和/或化学疗法的血液学辅助疗法的用途代表了IL- 12在癌症生物学中的新应用。