National Cancer Institute’s Fermentation Development Program
The present National Cancer Institute (NCI) fermentation antineoplastic development program is reviewed. The program regarding the isolation of microorganisms, their fermentation, screening productivity, antineoplastic structures of interest, and future plans follows.
NCI initiated its fermentation program in 1956 and, during the next four years, the primary organisms isolated and screened for their abilities to produce antineoplastic agents were fungi. Undoubtedly, the use of fungi was dictated by the early success of penicillin as an antimicrobial agent.  From 1960 to 1975, the isolation and fermentation of streptomycetes dominated the program. During this same period, Streptomyces were the most prolific organisms for the production of novel antimicrobial antibiotics, but this does not necessarily mean they would be the best producers of antineoplastic agents. During these years approximately 700 microbial metabolites, obtained by worldwide surveillance or by NCI sponsored research, were tested in various NCI in vivo screens (L1210, S180, Ca 755, Walker 256) While this research resulted in the discovery of several excellent antineoplastic antibiotics such as streptozotocin, mithramycin, adriamycin (Italian) and bleomycin (Japanese), it was decided that other unusual organisms might yield different, and possibly better, anticancer agents.
Streptomyces have been an excellent source of a number of antimicrobial antibiotics, however, under the test conditions previously used, these organisms have been a relatively poor source of antifungal or antiviral substances.  Results of the NCI program, during this period, indicated that the same agents were being rediscovered at a high rate. The program was redirected in late 1974. The emphasis was placed on obtaining a multitude of new organisms; to ferment them under unusual conditions, and to utilize more prescreens to obtain new types of structures. Hopefully, these efforts would increase the number of in vivo active beers and thus increase the total number of novel compounds isolated. Prescreens should conserve effort in that fewer fermentation broths would be subjected to in vivo testing. Prescreens may also identify new activities which might be caused by new chemical structures and simultaneously increase the efficiency of the in vivo tests. The following data summarizes the current NCI contract research program. However, since the materials isolated during 1975 and 1976 have not yet reached clinical trials, it is too early to obtain a good measure of success of the overall program. Preliminary data indicates success in obtaining novel antineoplastic agents active against animal tumors.
KeywordsNational Cancer Institute Fermentation Broth Antineoplastic Agent Infectious Bronchitis Virus Terminal Amine Group
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