Immunotherapy as Novel Treatment of Lung Cancer: A Systematic Review

Abstract

Lung cancer is the top cause of cancer-related fatalities in both men and women around the world, and the second most commonly diagnosed cancer in both men and women. For many patients, traditional chemotherapy (CT) fails to give long-term benefit. Moreover, newer medicines targeting activating mutations in EGFR or ALK have shown increased response rates over CT in the minority of patients with these mutations; however, the majority of patients do not have actionable mutations and will not benefit from targeted therapies. In addition, several combinations of chemotherapeutic medicines with the angiogenesis inhibitor bevacizumab have provided only minor additional benefits. However, immunotherapy using checkpoint inhibitors has shown to have a lot of potential in the treatment of advanced non-SCLC (NSCLC) in recent trials. These new medications encourage the host immune system to recognize tumor cells as foreign invaders and halting their growth. They help alleviate immune system suppression, which allows tumor development to be tolerated. In checkpoint immunotherapy, humanized monoclonal antibodies targeting checkpoint signals such as programmed cell death receptor (PD-1) and programmed cell death ligand are employed (PD-L1). The immune system can be triggered to fight the tumor by inhibiting these receptors and signals. Immunotherapy for advanced lung cancer has created a new paradigm of therapeutic options, with increased survival and response rates and a less severe but distinct side profile when compared to CT. The PD-1 inhibitors nivolumab and pembrolizumab, as well as the PD-L1 inhibitor atezolizumab, have been approved by regulatory authorities for the treatment of advanced NSCLC. Hence, the current review article focuses on the role of immunotherapy, newer agents used for checkpoint inhibitors in lung cancer, their epidemiology, risk factors, side-effect profiles, therapeutic indications, and their mechanism of action for the successful treatment of lung cancer.

Regulatory Challenges and Landscapes of Monoclonal Antibody Registration: Global Outlook

“…Antibodies, a key component, recognize and bind to specific molecules (antigens) on cell surfaces, like those of cancer cells. This binding flags the cells for immune responses, either attracting diseasefighting molecules or triggering processes leading to cell destruction [21] Monoclonal antibodies are designed to function diversely, some with multifaceted actions. Certain types can simultaneously lag cancer cell growth, induce cell-membrane destruction, inhibit cell growth, hinder blood vessel formation, block immune suppressors, directly attack cancer cells, deliver radiation or chemotherapy, and connect cancer and immune cells in various ways.…”

“…Ensuring uniformity and stability in large-scale production can be challenging, and even minor deviations can have profound implications for safety and efficacy. Stringent quality control measures must be established to guarantee that the final product meets the necessary safety and efficacy standards [21].…”

“…These ADAs can neutralize the therapeutic antibodies or induce adverse immune reactions, compromising the treatment's efficacy and safety. The challenge lies in devising strategies to minimize the generation of ADAs while preserving the therapeutic benefits [20,21].…”

“…Striking the delicate balance between maintaining structural integrity and optimizing pharmacokinetics is essential. Developing formulation strategies that mitigate potential challenges, such as aggregation or instability, is paramount to ensure the therapeutic efficacy and safety of the final product [20,21].…”

“…For monoclonal antibody therapeutics, the inherent unpredictability in raw materials and complicated production processes add extra levels of risk. The effective development of advanced medicines will depend on a thorough understanding of the causes of variation, their effects on final product quality, essential process parameters, and pertinent control measures [21,26].…”