Uses of IL-12 as a Hematological Adjuvant Cancer Therapy

描述(申请人提供)：拟议的第一阶段和第二阶段研究的长期和总体目标是将白细胞介素12(IL-12)作为一种血液辅助癌症治疗的商业用途发展到放射治疗、化疗和联合方法。这一目标如果实现，将通过减少目前实践中的癌症治疗方法的血液毒性，在治疗各种癌症方面取得更大的成功。此外，用于造血恢复的IL-12的开发可以消除目前在肿瘤学和血液学领域所采用的造血移植，即骨髓或干细胞移植的需要。更具体地说，拟议的第I期研究旨在评估使用IL-12作为对抗治疗的可行性，即作为血液辅助治疗，以减轻与各种癌症治疗方式相关的血液毒性。此外，由于IL-12已知具有显著的抗肿瘤和抗血管生成特性，使用IL-12促进造血恢复可能伴随产生更高的癌症缓解率和存活率。 申请者Neumedicines，LLC与南加州大学(USC)的科学家合作发现，IL-12在将受试者从全身致命辐射(TBI)中拯救出来方面是唯一有效的。只需在全身照射前或照射后立即单独注射一次低剂量的IL-12(不使用任何添加的血细胞)，即可获得几乎完全的存活率。此外，在IL-12治疗后没有观察到明显的毒性，因此，我们建议：1)IL-12可以作为放射和化疗的血液学辅助治疗(I期)，以及2)IL-12的这种辅助使用可能提供一种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很多，但还没有获得临床批准使用IL-12治疗癌症。鉴于已知的IL-12的抗肿瘤和抗血管生成的特性，我们推测，将IL-12与放射治疗和/或化疗结合使用，将使治疗方案得以开发，从而在改善造血恢复的同时，产生更大的肿瘤缓解和存活率。IL-12作为血液学辅助治疗在放射治疗和/或化疗中的应用代表了IL-12在肿瘤生物学中的新应用。

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.