Table 4.

Comparison of Various PD-1/PD-L1 Monoclonal Antibodies – Mechanistic Action, Pros, and Cons.

Monoclonal Antibody	Mechanism of Action	Clinical Approvals	Advantages	Disadvantages
Pembroluzimab (Keytruda)	PD-1 mAb, inhibits PD-1 binding to PD-L1 or PD-L2	FDA-approved for metastatic non-small-cell lung cancer (2016) and unrespectable or MSI-H mCRC (2020).	Enhances the recognition of tumor cells by cytotoxic T cells.	Some patients show resistance and immunosuppressive activity of infiltrating immune cells.
Avelumab	Anti-PD-L1 antibody, blocks PD-1 receptors and B7-1 on T cells. stimulates antibody-dependent cell-mediated cytotoxicity via engineered Fc gamma receptor 1.	FDA-approved for metastatic Merkel cell carcinoma and locally advanced or metastatic urothelial carcinoma.	Promising clinical efficacy and satisfactory survival outcomes observed in various cancers (NSCLC, thymoma, GC/gastroesophageal cancer, ovarian cancer, melanoma, and thyroid cancer).	Limited data on combination therapies and specific patient populations.
Nivolumab	PD-1 IgG4 mAb, inhibits PD-1 interaction with PD-L1 and PD-L2.	FDA approved for various cancers, including advanced melanoma (2014), 2017 for the second-line treatment of MSI-H/dMMR CRC, NSCLC, renal cell carcinoma, Hodgkin’s lymphoma and CRC	High affinity binding, effectively blocking the interaction between PD-1 receptors on T cells and their ligands (PD-L1 and PD-L2) on tumor cells, thus restoring T-cell activity Significant clinical activity observed in specific patient populations.	Primary resistance occurs in some cases, and not all CRCs respond to immunotherapy.
Budigalimab (ABBV-181)	PD-1 IgG1 mAb, modified for reduced FcγR interaction	Investigational, not FDA approved	Potent PD-1-blocking activity and high specificity. well tolerated and safe with high efficacy.	Not FDA approved Ongoing clinical trials is needed to provide more insights.
Tislelizumab (BGB-A317)	PD-1 IgG4 mAb	FDA approved for esophageal cancer, hepatocellular carcinoma (2019), and GC/gastroesophageal cancer (2020)	High affinity to PD-1 leading to potent T-cell activation and antitumor immune responses The structure has been modified to maximize its ability to inhibit PD-1/PD-L1 interactions and minimize its binding to FcγR, which is a potential mechanism of resistance to anti-PD-1 therapy	Not yet approved by the FDA for CRC treatment
Dostarlimab (JEMPERLI)	PD-1 IgG4- mAb, inhibits PD-1 interaction with PD-L1 and PD-L2	FDA approved for dMMR recurrent or advanced endometrial cancer (2021)	Low need for Fc activity, making it suitable for use as a functional antagonist. Improves Teff activities in vitro by increasing cytokine generation. Demonstrated effectiveness in several cancers, including dMMR pan malignancies, second-line dMMR endometrial cancer, and NSCLC.	Limited data on efficacy and safety in CRC. Ongoing trials are needed to provide more insights.
Atezolizumab	Anti-PD-L1 IgG1 mAb	FDA approved for metastatic NSCLC (2016)	High-affinity against PD-L1. Potential benefit in combination with specific regimens. Has the potential to augment the immune system’s antitumor response while impeding the proliferation and metastasis of malignant cells. The combination of chemotherapy and other drugs may yield superior outcomes in the management of mCRC.	Limited benefit observed in some combination therapies. Ongoing studies are required to refine predictive biomarkers.
Durvalumab (Imfinzi)	Anti-PD-L1 IgG1 mAb Blocks PD-1/PD-L1 interaction	FDA approved for urothelial carcinoma (2017), NSCLC (2018), ES-SCLC (2020)	Promising response rates and satisfactory survival outcomes in patients with mCRC.	Limited clinical response and safety concerns underscore the need for ongoing research and refinement of predictive biomarker. More research is required to enhance the efficacy in certain patient groups.