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Novel immune check point inhibiting antibodies in cancer therapy-Opportunities and challenges
Yael Diesendruck1, Itai Benhar1
1Department of Molecular Microbiology and Biotechnology, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv 69978, Israel.
Abstract:
Drug resistance of tumor cells to chemotherapy is limiting the therapeutic efficacy of most anticancer drugs and represents a major obstacle in medical oncology. However, treatment of various human malignancies with biologics, mostly monoclonal antibodies (mAbs), is not limited by such chemoresistance mechanisms. However, other resistance or evasion mechanisms limit the efficacy to anticancer therapeutic mAbs that engage tumor-associated antigens on the surface of the malignant cells. Immune checkpoint blocking monoclonal antibodies are heralded as a promising therapeutic approach in clinical oncology. These mAbs do not directly attack the malignant cells as most anticancer mAbs; rather, they enhance the anti-tumor response of the immune system by targeting immune regulatory pathways. Three mAbs targeting immune checkpoint molecules are currently used in the clinic and new mAbs that target other potential inhibitory targets are being actively investigated. This therapeutic approach, while proving as highly beneficial for many patients, is prone to toxicities and side effects of an autoimmune nature. Defining suitable management algorithms and biomarkers that predict therapeutic effects and adverse toxicity are required to provide survival benefit for larger numbers of cancer patients. Overcoming these challenges, along with opportunities for new agents and combinatorial strategies are the main focus of immune checkpoint blockade research today.
Insights
Cancer treatment faces challenges with drug resistance and monoclonal antibody (mAb) efficacy. Immune checkpoint blocking mAbs offer promise but require management strategies for autoimmune toxicities and improved patient outcomes.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Chemotherapy resistance limits anticancer drug efficacy.
- Therapeutic monoclonal antibodies (mAbs) face resistance via tumor-evasion mechanisms.
- Immune checkpoint blocking mAbs enhance anti-tumor immunity but can cause autoimmune toxicities.
Purpose of the Study:
- To review the challenges and opportunities in immune checkpoint blockade therapy.
- To highlight the need for management algorithms and predictive biomarkers for mAb treatments.
Main Methods:
- Review of current clinical applications of immune checkpoint blocking mAbs.
- Investigation of novel targets and combinatorial strategies for immune checkpoint blockade.
- Analysis of resistance and toxicity mechanisms associated with therapeutic mAbs.
Main Results:
- Three mAbs targeting immune checkpoints are approved for clinical use.
- Research is ongoing for new mAbs and combination therapies.
- Identifying biomarkers for efficacy and toxicity is crucial for patient benefit.
Conclusions:
- Immune checkpoint blockade is a promising cancer therapy, but challenges remain.
- Management algorithms and predictive biomarkers are needed to optimize treatment.
- Future research focuses on overcoming resistance and toxicity for broader patient survival benefit.