Stimulation of hematopoietic stem cells by interferon inducer in nonhuman primates receiving fractionated total body irradiation

30 ARS 63rd Annual Meeting

Radiation Oncology @ Biology o Physics

(21) STIMULATION OF HEMATOPOIETIC IN NONHUMAN PRIMATES RECEIVING

STEM CELLS BY INTERFERON FRACTIONATED TOTAL 90DY

E. Lvovsky,

M.D.1, 2. Bengali,

Ph.D.*,

J.Robinson,

Ph.D.1,

B.S.l,

Department Marylandl,

N. Bautro,

of Radiation Litton

Bionetics,

Therapy,

P. Levine,

M.D.3 , S. Leiseka,

H. Levy, Ph.D.3,

University

Maryland’

Bethesda,

Maryland3

M,D.3,

and R. Scott,

of rviaryland

Kensington,

INDUCER IRRADIATION

, National

Hospital, Institutes

ivl.D.1

Baltimore, of Health,

The importance of selective protection of bone marrow (BM) during !arge field and total body irradiation (TBI) used in treatment of disseminated neoplastic disorders is well recognized. Radioprotective agents, while effective in laboratory animals are prohibitively toxic in protective concentrations in primates or offer equal protection to neoplastic cells. Therefore, the recent demonstration by us of radioprotection by interferon (IF), an antiviral and antineoplastic agent, has open experimental opportunities of developing compounds with more selective action. Such a compound, polyICLC - a complex of 9S polyinosinic: 9S polcytidilic acid with 27 000 LMWpoly-L-lysine and carboxymethylcellulosewas able to induce IF in rodents and primate including man, and was shown to be radioprotective in mice. The radioprotection in mice was associated with increased differentiation of hematopoietic stem cells-colony forming cells (CFC). The maximum of BcM protection by polyICLC was observed when TBI was given immediately after peak IF response or 24 hours after polyICLC. To extend these observations the present study was undertaken using nonhuman primates. In this study, BM protection by polyICLC together with IF response was evaluated in Rhesus monkeys receiving TBI. TBI was delivered in 50 rad fractions two times a week to a total of 250 rad at midplane. As a radiation source 4 .MeV linear accelerator was used. Eleven adult (5-7kg) Healthy Rhesus monkeys were divided into three groups as follows: 5 received polyICLC and TBI, 4- only TBI and two- only polyICLC. PolyICLC was given I.V. at 0.3 mg/kg BW, During TBI treatment and six weeks thereafter BM morphology and number of CFC was studied. The number of blood elements, IF titers and polyICLC levels in serum were also followed. Data obtained in this study showed inhibition of BM in both treated groups During second week postirradiation the number of CFC in after 150 rad TBI. polyICLC-TBI monkeys and TBI group had a ratio of 13:1, indicating stimulatory effect of the interferon inducer on hematopoietic stem cells. The detailed results will be discussed in this report.

(22) Arnold

MYMOSIN ALPHA-l IN MALIGNANT GLIOMAS: AUGMENTATIONOF IMMUNEREACTIVITY IN A PHASE I STUDY M.D.l*, Ayub K. Omnaya, M.D.2, Paul 8. Chre&ien, M.D.3, John McClure, Ph.D.4, and Allan L. Goldstein, Ph.D.

M. Baskies,

1. Department of Surgery, Boston University School of Medicine, Boston, Ma., 2. Section of Applied Neurosurgical Research, NINCDS and 3. Surgery Branch, NCI, Bethesda, Md., 4. Department of Biochemistry, George Washington University School of Medicine, Washington D.C. Thymosin fraction 5 (f5), an extract of thymus gland consisting of multiple polypeptides isolated by A.!_. Goldstein augments cellular immunity in experimental animals and humans with cellular immune deficiencies. In a preliminary study, we found improved survival among patients with impaired cellular immunity who received thymosin f5 (Cancer 43:863, 1979). Thymos'n aI, one of the Puri-