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Abstract:
Biological response modifiers (BRMs) are agents or approaches that modify the relationship between the tumor and host by modifying the host's biological responses to tumor cells, with resultant therapeutic effects. BRMs include immunomodulators and components of the immune system, e.g. cytokines, antibodies and effector cells. A central challenge in the development of BRMs for therapy of cancer patients is to determine the main mechanism of action of each agent and by monitoring for effects of treatment on the key parameters, optimize the treatment protocol. The experience to date with interferons and with interleukin-2 (IL-2) is summarized, to illustrate both the promise of BRMs and the difficulties in determining the optimal therapeutic regimen and in turn this potential for more effective treatment of cancer. A new sequence of clinical trials for clinical evaluation of BRMs is described, with an emphasis on treatment of patients with minimal tumor burden.
Insights
Biological response modifiers (BRMs) enhance cancer treatment by modulating the host
Area of Science:
- Oncology and Immunology
Background:
- Biological response modifiers (BRMs) modulate the host-tumor relationship for therapeutic benefit.
- BRMs encompass immunomodulators, cytokines, antibodies, and effector cells.
- Optimizing BRM therapy requires understanding mechanisms of action and monitoring treatment effects.
Purpose of the Study:
- To summarize the therapeutic potential and challenges of BRMs in cancer treatment.
- To illustrate these points using examples of interferons and interleukin-2 (IL-2).
- To propose a new clinical trial sequence for evaluating BRMs, particularly in patients with minimal tumor burden.
Main Methods:
- Review of existing data on interferons and IL-2.
- Analysis of challenges in determining optimal therapeutic regimens for BRMs.
- Description of a novel clinical trial design for BRM evaluation.
Main Results:
- Interferons and IL-2 show promise but present difficulties in optimizing treatment.
- Determining mechanisms of action is crucial for effective BRM therapy.
- A new trial sequence focuses on patients with minimal tumor burden.
Conclusions:
- BRMs offer a promising avenue for cancer therapy.
- Optimizing BRM treatment requires a deeper understanding of their mechanisms and careful monitoring.
- New clinical trial designs are needed to effectively evaluate BRMs, especially in early-stage disease.