Related Experiment Videos
Chemotherapeutics: a questionable or a promising project
Abstract:
While repository adjuvants are already established drugs for antigen specific immunomodulation, no unspecific active immunomodulator has successfully passed clinical trials in tumor patients in Western countries yet. As this is in striking contrast to the effects seen with unspecific immunomodulators in experimental immunological and tumor test systems, the value of those screening models to predict clinical success may be asked for. To improve the success rate, it is recommended to test compounds for their immunomodulatory effects as broad as possible in ex vivo and in vivo test systems. Subsequently, the prophylactic as well as therapeutic potency of selected immunomodulating drugs should be evaluated in various models of aptitude, such as chronic infection, autoimmune diseases and chronic inflammatory reactions. Those diseases are at least to a certain extent influenced by the immune system, in contrast to the uncertainty in case of tumor diseases. In a battery of chronic infection models we could find that different chemoimmunotherapeutics with very similar immunopharmacological activity behaved quite different. Most compounds were ineffective, a part enhanced chronic diseases and only in a few cases a therapeutic effect could be shown. On the other hand, effectivity in protection against the pathogenicity of subsequently applied, selected microorganisms does not predict the therapeutic potency for the same pathogen. Altogether the data show that activation of cells of the immune system by an immunostimulating drug does not predict its therapeutic potency. Moreover, activation of immune cells may also impair the immune resistance.
Insights
Unspecific immunomodulators show promise in lab studies but often fail in human cancer trials. Immune cell activation does not guarantee therapeutic effect, and can sometimes harm immune resistance.
Area of Science:
- Immunology
- Pharmacology
- Oncology
Background:
- Repository adjuvants are established for specific immunomodulation.
- No unspecific active immunomodulator has succeeded in Western clinical trials for cancer patients.
- A discrepancy exists between the efficacy of unspecific immunomodulators in experimental models and clinical outcomes.
Purpose of the Study:
- To evaluate the predictive value of experimental models for clinical success of unspecific immunomodulators.
- To recommend improved strategies for testing immunomodulatory compounds.
- To assess the prophylactic and therapeutic potential of immunomodulating drugs in various disease models.
Main Methods:
- Testing compounds for broad immunomodulatory effects using ex vivo and in vivo systems.
- Evaluating prophylactic and therapeutic potency in chronic infection, autoimmune disease, and chronic inflammatory reaction models.
- Comparing the performance of chemoimmunotherapeutics with similar immunopharmacological activity in chronic infection models.
Main Results:
- Different chemoimmunotherapeutics with similar immunopharmacological activity showed varied outcomes in chronic infection models.
- Most compounds were ineffective; some exacerbated chronic diseases, and only a few demonstrated therapeutic effects.
- Efficacy in protection against pathogens did not predict therapeutic potency for the same pathogen.
Conclusions:
- Activation of immune cells by immunostimulating drugs does not reliably predict therapeutic efficacy.
- Immune cell activation may potentially impair immune resistance.
- Current experimental models may not accurately predict the clinical success of unspecific immunomodulators in cancer therapy.