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[Tumoricidal biological response modifiers (BRM)]
Y Niitsu1, Y Kohgo, N Watanabe
1Dept. of Internal Medicine (Section 4), Sapporo Medical College.
Abstract:
TNF, IFN, LT and IL-1 are well-known biological response modifiers (BRM) with cytocidal activity. Whereas carcinostatic agents generally derive their cytocidal action from their direct mutual reaction with target molecules (e.g., DNA, RNA), the cytocidal action of BRM resides in the enzyme response which ensures upon their binding to receptors. Accordingly, concomitant use of these drug of differing mechanism of action has a rationale. Considering that a certain kind of counteracting protein is present in cancer cells which are refractory or resistant to such cytokines, combination therapy with carcinostatic agents with inhibitive activity against such protein is also justified. In the same context the effects of TIL and LAK activated by IL-2 could be enhanced if the immune system should be modulated by combined use of BRM and carcinostatic agents such as CY. This paper discusses the results obtained with BRM and carcinostatic agents in combination in animal models and clinical cases.
Insights
Combining biological response modifiers (BRMs) like TNF and IFN with carcinostatic agents offers a rational approach to cancer treatment. This strategy enhances anti-cancer effects by targeting tumor cells through distinct mechanisms and overcoming resistance.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Context:
- Biological response modifiers (BRMs) such as Tumor Necrosis Factor (TNF), Interferon (IFN), Lymphotoxin (LT), and Interleukin-1 (IL-1) possess inherent cytocidal activity against cancer cells.
- Unlike conventional carcinostatic agents that directly interact with cellular targets like DNA/RNA, BRMs elicit their cytotoxic effects through receptor-mediated enzyme responses.
- Cancer cells can develop resistance to BRMs due to counteracting proteins, necessitating alternative therapeutic strategies.
Purpose:
- To explore the rationale and efficacy of combining BRMs with carcinostatic agents for cancer therapy.
- To investigate combination therapies that leverage distinct mechanisms of action to enhance anti-cancer outcomes.
- To evaluate the potential of modulating the immune system through combined BRM and carcinostatic agent administration, including enhancing T-cell-based immunotherapies like TIL and LAK activated by IL-2.
Summary:
- The cytocidal action of BRMs is mediated by enzyme responses triggered upon receptor binding, distinct from the direct molecular interactions of carcinostatic drugs.
- Combination therapy is rationalized by the differing mechanisms of action of BRMs and carcinostatic agents, and by targeting resistance mechanisms in refractory cancer cells.
- The paper reviews findings from animal models and clinical cases examining the combined use of BRMs and carcinostatic agents, including cyclophosphamide (CY), to enhance immune responses and therapeutic effects.
Impact:
- Demonstrates the synergistic potential of combining immunomodulatory and cytotoxic agents in cancer treatment.
- Provides a scientific basis for developing novel combination therapies to overcome drug resistance and improve patient outcomes.
- Highlights the importance of understanding cellular response mechanisms for optimizing cancer treatment strategies.
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