Uses of IL-12 as a Hematological Adjuvant Cancer Therapy

描述（由申请人提供）：拟议的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）的商业用途，作为放射治疗、化疗和联合方法的血液辅助癌症治疗。这一目标，如果实现，应该产生更大的成功治疗各种癌症通过减少血液学毒性目前实践的癌症治疗方式。此外，开发用于造血恢复的IL-12可以消除对造血移植的需求，即骨髓或干细胞移植，如目前在肿瘤学和血液学领域的实践。更具体地说，拟议的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促进造血恢复可能同时产生更高的总体癌症缓解和生存率。

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.