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“Studies on the supression of immune responses by the periwinkle alkaloids vincristine and vinblastine”. 
J Clin Invest. 1964 Dec;43:2394-403.
It has been possible to achieve chemical suppression of immunological responsiveness by several classes of compounds. The most successful drugs used in the past have been the alkylating agents (1), the antipurines (2), the folic acid antagonists (3, 4), and actinomycin D (5, 6). Further study of the problem of chemical immune suppression is warranted both because of the fundamental information about immune responsiveness that may be gained from such investigations and because of the continuing clinical need for effective agents. In the present report we described our results in the rat with vincristine and vinblastine,' examples of a new class of immunosuppressive drugs (7). Derived from the common periwinkle plant Vinca rosea and chemically characterized as dimeric alkaloids containing both the indole and dihydroindole moieties (8), the compounds were discovered independently by Noble, Beer, and Cutts (9)2 and a group of investigators including Johnson, Armstrong, Gorman, and Burnett (8,10).3 Because these drugs have been shown to be effective against a variety of experimental ( 11) and human lymphoid neoplasms (8, 12, 13), it appeared logical to try them as inhibitors of immune responses. We have found that not only do they inhibit antibody formation, delayed hypersensitivity, and homograft rejection, but they promptly suppress established delayed hypersensitivity. Furthermore, since one of the drugs * Submitted for publication November 13, 1963; accepted August 28, 1964. This investigation was supported by grant CA-07179 from the National Cancer Institute. This is publication no. 1185 of the Cancer Commission of Harvard University. 1 Both obtained from Lilly Laboratories, Indianapolis, Ind. 2At the University of Western Ontario, London, Ont. 3 At Lilly Laboratories, Indianapolis, Ind. (vinblastine) produces marked leukopenia and the other (vincristine) does not (8), an opportunity was afforded to assess the role of the circulating lymphocyte in the several forms of immune responsiveness.
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