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Audrey Simonaggio1, Aurélien Marabelle2
1Gustave Roussy, Université Paris-Saclay, département d'innovation thérapeutique et d'essais précoces, Villejuif, F-94805, France.
Alternative Immunotherapies:
Monoclonal antibodies targeted at immune checkpoint molecules such as PD-1, PD-L1, and CTLA-4 have revolutionized the field of oncology in a few years. This success is explained by the large spectrum of activity of these therapies (more than 30 different cancer types), and the durability of tumor responses which provide benefits in overall survival for patients. However, a majority of patients do not respond to these treatments and novel immune strategies are needed to overcome resistance to monotherapies. A compelling effort is ongoing with numerous novel immunotherapies being in clinical development. Beyond immunomodulatory antibodies, other immunotherapies (small inhibitory molecules, vaccines, cytokines, viruses, cells) are in clinical trials or have been already approved, not only targeting T-cells but also other immune cells, including innate immune cells. This review summarizes the recent advances obtained with these new therapies.
Insights
New immunotherapies beyond immune checkpoint inhibitors are crucial for cancer patients who do not respond to current treatments. These alternative therapies target various immune cells, offering new hope for durable tumor responses and improved survival.
Area of Science:
- Oncology
- Immunology
- Cancer Therapeutics
Background:
- Immune checkpoint inhibitors (ICIs) like PD-1, PD-L1, and CTLA-4 antibodies have transformed cancer treatment, showing broad activity across many cancer types.
- Despite ICI success, a significant portion of patients exhibit resistance, necessitating the development of novel immunotherapeutic strategies.
- Durable responses and improved overall survival are key benefits observed with current immunotherapies.
Purpose of the Study:
- To review recent advancements in alternative immunotherapies for cancer treatment.
- To explore novel strategies beyond established immune checkpoint blockade.
- To summarize emerging therapies targeting both T-cells and innate immune cells.
Main Methods:
- Review of clinical trials and recent literature on novel immunotherapies.
- Analysis of therapies including small molecules, vaccines, cytokines, viruses, and cellular therapies.
- Focus on therapies targeting a broader range of immune cells, including innate immunity.
Main Results:
- Numerous novel immunotherapies are in clinical development, expanding treatment options.
- These alternative therapies encompass diverse mechanisms beyond immune checkpoint modulation.
- Emerging treatments are designed to overcome resistance to monotherapies and broaden efficacy.
Conclusions:
- Alternative immunotherapies are essential to address unmet needs in patients resistant to current treatments.
- The development pipeline includes a wide array of agents targeting diverse immune pathways.
- Future cancer treatment will likely involve a combination of strategies to enhance anti-tumor immunity.