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.
Thesaurus Terms: immunomodulator, interleukin 12, neoplasm /cancer immunotherapy, therapy design /development combination cancer therapy, hematology, neoplasm /cancer chemotherapy, neoplasm /cancer radiation therapy, oncology, whole body imaging /scanning laboratory mouse
