Evaluation of Immunomodulatory and Therapeutic Properties of Biological Response Modifiers: A Comparison of Preclinical and Clinical Studies

Induction of antitumor L3T4-positive T cells by OK-432 at tumor sites in mice

“…It has been reported that OK-432 augmented various immunological cells including neutrophils [22,25] macrophages [13] and NK [18,23] cells and cytotoxic T cells [5], all of which have been shown to be cytotoxic against tumor cells in vitro and might work for tumor eradication in vivo. We have reported previously that a successful OK-432 treatment protocol for syngeneic tumor in euthymic mice failed to work against tumors in athymic mice [14].…”

“…Clinical studies have shown that OK-432, when administered to cancer patients after surgical treatment or chemotherapy, is effective in significantly prolonging their disease-free periods and/or survival time [20,22,24]. Many experimental studies with OK-432 have demonstrated that its antitumor effects could be caused by activation of various immunocompetent cells including augmentation of natural killer (NK) activity [18,23] and induction of cytotoxic macrophages [13], cytotoxic polymorphonuclear cells [4,8,21,25] and cytotoxic T lymphocytes [5]. Despite extensive studies of OK-432, the exact mechanism of the antitumor effects and the optimum dosage and route of administration for the best therapeutic efficacy remain to be further clarified.…”

Comparison of immunomodulatory and immunotherapeutic properties of biologic response modifiers

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This chapter focuses on the study of a wide variety of biologic response modifiers (BRMs) that have been tested by the Preclinical Screening Laboratory [12,17,[23][24][25]. These compounds include interferon inducers, natural extracts and products, small molecule weight chemicals and polypeptides, thymosins, and recombinant lymphokines such as interferons and interleukin 2.

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“…The Preclinical Screening Laboratory (PSL) was established for the same reason as the NCIs drug development program, i.e., there was a need to evaluate the therapeutic potential of a variety of agents and to select the most promising agents for clinical trials [9,13,20,35,36]. The in-depth evaluation of the immunomodulation and therapeutic potential of even a moderate number of BRMs has been a formidable task [23,25]. The PSL utilizes a series of in vitro and in vivo models [31] that were selected for their expected relevance to the immunotherapy of neoplastic disease.…”

“…The PSL utilizes a series of in vitro and in vivo models [31] that were selected for their expected relevance to the immunotherapy of neoplastic disease. Each of the assays has been carefully standardized so that consistent and reproducible effects are observed.We also utilize sequential and more demanding series of assays, designed to determine the range of immunomodulatory effects of a BRM as well as to evaluate its therapeutic potential [ 12,17,[23][24][25]. The initial emphasis is on defining the effect of potential BRMs on T cells, B cells, N K cells, and macrophages.…”