Innovate Immune Checkpoint Inhibitors- Time for New Therapies
Immune Checkpoint Inhibitors
Immune checkpoint inhibitors (ICIs) are a groundbreaking class of drugs that activate T-lymphocyte-mediated antitumor responses. Over the past decade, they have revolutionized cancer treatment and extended survival for patients with various tumor types. As of December 2021, over 5600 ICI-related clinical trials were ongoing, with total revenue reaching $60 billion. However, the success of ICIs has not been without challenges, such as redundant trials, high costs, and limited efficacy in some hematologic cancers.
Toxicity and Autoimmunity
ICIs can cause significant toxic effects and provoke autoimmunity in some patients, resulting in adverse events in the lungs, liver, and skin. These adverse events can lead to a 1% fatality rate, highlighting the need for better understanding and management of the toxic effects of ICIs. Clinicians must identify patients at higher risk for toxicity and determine the most effective treatments for these patients.
Biomarkers and Precision Medicine
Despite the success of ICIs, there is a lack of biomarkers to accurately identify patients who may respond to treatment. In the age of precision medicine, there is a need for more refined approaches that can target specific cancer antigens without the global toxicity of ICIs.
Emerging Immunotherapy Options
New options in immunotherapy are being developed to enhance specificity and reduce toxicity. One promising approach involves activating more tumor-specific and less toxic T-cell populations. Clinical trials of variable beta (Vβ)-activating human antibodies are currently underway, and this approach may prove to be important for new treatments for T-cell lymphoma and leukemia.
Other promising strategies include CAR T-cell therapies for T-cell cancers, CAR-NK cell therapies, bispecific antibodies targeting the T-cell receptor β chain, and combining ICIs with radiation therapy.
Regulatory Considerations and Future Directions
The future of immunotherapy research should focus on developing antigen-specific, less toxic T-cell–based approaches and exploiting T-cell memory for more durable antitumor effects. Regulatory agencies could consider implementing a bioequivalency standard to reduce redundancy in clinical trials. Encouraging the pharmaceutical industry to invest in innovative technologies addressing the shortcomings of current ICI-based therapies is essential for further advancement in cancer treatment.