Next-Generation Immunotherapy in Cancer: Mechanisms, Limits, Risks
Next-generation immunotherapy in cancer is considered a modern approach that specifically modulates the immune system to improve the recognition and elimination of tumour cells. In certain cases, it shows pronounced effects; however, it is not effective for all patients and may be associated with significant risks.
In today’s article, we examine how immunotherapy in cancer works, what it can achieve — and what it cannot.
Why Immunotherapy in Cancer Is Now in Focus?
Cancer is no longer viewed solely as the result of genetic alterations, but as an interaction between tumours and their environments. The immune system is a central component of the tumour microenvironment and plays a decisive role in how tumours develop and respond to therapeutic interventions — an aspect that is crucial for understanding modern immunotherapies (Hanahan & Weinberg, 2011).
How Does Next-Generation Immunotherapy Work at the Cellular Level?
Cancer immunotherapy does not primarily target the tumour cell itself, but rather modulates those mechanisms of the immune system that determine whether tumour cells are recognised and attacked.
Under normal conditions, the immune system is capable of identifying and eliminating abnormal cells. However, tumours can develop strategies to evade this control, for example by emitting inhibitory signals or actively suppressing immune responses.
Important approaches:
· Checkpoint inhibitors block inhibitory signalling pathways (e.g. PD-1 or CTLA-4), which normally act as “brakes” on the immune system. By blocking these pathways, immune cell activity can be restored, allowing tumour cells to be recognised and attacked again.
· CAR T-cell therapies involve the targeted genetic modification of immune cells outside the body. These modified cells are then reinfused into the patient. They are able to recognise and attack tumour cells in a targeted manner.
These approaches can lead to renewed recognition and elimination of tumour cells. However, therapeutic success depends not only on the tumour itself, but also on how effectively the immune system responds to these interventions (Pardoll, 2012).
What Does This Mean in Clinical Practice?
The application of immunotherapies varies depending on the method, but generally follows certain procedures (Brahmer et al., 2018; June et al., 2018):
· Checkpoint inhibitors are usually administered on an outpatient basis in specialised oncology clinics via infusion, typically every 2 to 4 weeks over several months. The duration depends on the individual treatment response.
Regular medical monitoring is required between treatments, as side effects may occur with a delay.
· CAR T-cell therapy is significantly more complex and is carried out in specialised centres on an inpatient basis. Following the extraction of immune cells (leukapheresis), the cells are genetically modified in the laboratory. This is followed by chemotherapy to prepare for reinfusion of the modified cells. The infusion itself requires a hospital stay of several days or even weeks.
Typical risks, such as cytokine release syndrome (an excessive immune response that can lead to fever, circulatory problems and systemic inflammation), make inpatient monitoring necessary.
Next-Generation Immunotherapy: Risks and Side Effects
Immunotherapy can be associated with significant adverse effects, including:
- autoimmune reactions
- inflammatory processes in organs
- systemic immune reactions
(Postow et al., 2018; Wang et al., 2018).
Next-Generation Immunotherapy: A Progress — but with Limitations
Any evaluation of new immunotherapies reveals a heterogeneous picture: as studies show, only a proportion of patients benefit, while others experience insufficient effects (Topalian et al., 2012).
Resistance mechanisms can also significantly limit treatment success (Sharma et al., 2017).
An Assessment: What We Know and What We Don’t
The long-term effects of cancer immunotherapy are not yet fully understood. While some patients show sustained responses, robust long-term data are lacking for many applications (Sharma et al., 2017).
Next-generation immunotherapy represents progress, but does not resolve the fundamental complexity of cancer. Its effectiveness depends on factors such as tumour type, immune responses and the tumour microenvironment.
Conclusion: The Next Generation Gives Hope
These therapeutic approaches demonstrate that the immune system is a central target in cancer treatment. In certain cases, they can lead to substantial therapeutic success — particularly where conventional approaches reach their limits.
At the same time, the effectiveness of next-generation immunotherapies is highly dependent on the individual disease profile and cannot be reliably predicted. Concerns about incomplete long-term data are compounded by potentially significant side effects.
It remains desirable — though not yet fully clarified whether and how — to integrate such therapies into a more comprehensive understanding of cancer. An understanding that more strongly takes into account the complex interactions between tumour, immune system and metabolism.
FAQ – Frequently Asked Questions About Cancer Immunotherapies
1. Why are cancer immunotherapies often described as a “breakthrough” despite limited effectiveness?
Because the limited overall response rate often receives little attention in public discourse, while treatment successes are highlighted more prominently.
2. What role does the individual baseline condition play in treatment success?
Factors such as immune status, tumour microenvironment and genetic characteristics significantly influence whether immunotherapy is effective at all.
3. Why is it difficult to predict success in immunotherapy?
Because the underlying biological processes are complex and not yet fully understood.
4. Can immunotherapies permanently alter the immune system?
This is possible, but not yet conclusively established. Long-term effects on the immune system are still under investigation.
5. Why are next-generation immunotherapies already widely used despite open questions?
Because significant therapeutic successes can be achieved in certain cases (illustrating the typical tension between clinical application and incomplete evidence).
Further information on cancer treatment can be found in the respective volume of our “Medizinskandale” series as well as in the volumes of our “Codex Humanus.” The fifth volume has recently been published. Feel free to visit our online shop. Our other blog articles also provide additional insights into these and many other topics.
Sources:
· Hanahan, D.; Weinberg, R. A. (2011): “Hallmarks of cancer: The next generation,” Cell.
· Pardoll, D. M. (2012): “The blockade of immune checkpoints in cancer immunotherapy,” Nature Reviews Cancer.
· Brahmer, J. R. et al. (2018): “Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy,” Journal of Clinical Oncology.
· June, C. H. et al. (2018): “CAR T cell immunotherapy for human cancer,” Science.
· Postow, M. A. et al. (2018): “Immune-Related Adverse Events Associated with Immune Checkpoint Blockade,” New England Journal of Medicine.
· Wang, D. Y. et al. (2018): “Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis,” JAMA Oncology.
· Topalian, S. L. et al. (2012): “Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in Cancer,” New England Journal of Medicine.
· Sharma, P. et al. (2017): “Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy,” Cell.