However, before the commercialization of plant-produced pembrolizumab and nivolumab can take place, it is crucial to complete both in vitro and in vivo screening to ensure that the same structure and activity are exhibited in those that are already commercially available [16,17]. 5.4. pembrolizumab, nivolumab, molecular farming 1. PTGS2 Introduction Cancer is one of the leading causes of mortality worldwide and accounted for almost 10 million deaths in 2021 [1]. According to the World Health Business, lung, colorectum, liver, belly and breast malignancy resulted in the majority of these cancer-related mortalities [2]. Approximately 70% of these deaths occurred Apatinib in low- and middle-income countries (LMICs), reflecting a significant space in the availability of comprehensive therapeutics [1,3]. Previous literature has shown that the convenience of comprehensive cancer Apatinib treatments is usually less than 15% in LMICs, but greater than 90% in high-income countries Apatinib [2]. With the incidence of malignancy diagnoses estimated to increase by 47% by 2040, there is an increasing requirement to improve the efficacy of current treatments while promoting convenience for cancer patients in LMICs [1]. The conventional armamentarium of malignancy treatment includes the use of surgery, radiation, and particularly chemotherapy [4]. However, chemotherapeutic brokers are not specific for tumorigenic cells, and thus also damage non-tumorigenic cells in the body, resulting in a plethora of side effects, including fatigue, diarrhea, myelosuppression, neutropenia and in some cases, death [5]. Thus, a considerable amount of research has focused on the development of novel targeted therapies, including monoclonal antibodies (mAbs) that bind specific tumor surface proteins and stimulate the immune system against tumorigenic cells [6,7]. Immunotherapy is usually a promising malignancy therapy capable of activating the immune system or attenuating the immunosuppressive effects of tumorigenic cells [8,9]. Immune checkpoint inhibitors (ICIs) are one class of immunotherapeutics that have exhibited high clinical success rates and function by inhibiting immune checkpoints between tumorigenic cells and cluster of differentiation 8 (CD8) T lymphocytes [10]. Furthermore, the most frequently targeted immune checkpoint for malignancy therapy includes the programmed cell death protein 1 (PD-1) and the programmed death-ligand 1 (PD-L1) pathway [11]. PD-1 is usually a receptor found on T lymphocytes and binds to its ligand PD-L1 generally overexpressed in several types of malignancy including lung-, pancreatic-, gastric- and ovarian malignancy [11,12]. Ultimately, the binding of PD-1 to PD-L1 prevents the proliferation of T lymphocytes, inhibits cytokine production and results in the induction of apoptosis via the inhibition of survival- and growth signaling pathways including the Phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)- and the rat sarcoma (RAS) pathway [13,14]. Therefore, PD-1 is an integral component involved in the progression and survival of tumorigenic cells [14]. The most frequently used ICIs currently on the market include pembrolizumab (Keytruda?) and nivolumab (OPDIVO?), which are both anti-PD-1 mAbs [15]. These two mAbs bind with high affinity to PD-1 on T lymphocytes and thereby inhibit the binding of PD-L1 on tumorigenic cells [11,12]. The latter leads to the activation of T lymphocytes, resulting in the induction of apoptosis in tumorigenic cells through T-cell-mediated cytotoxicity [11]. Nonetheless, the extortionate price of pembrolizumab and nivolumab attributable to the mammalian cell production platform used to produce these two therapies makes them hardly accessible in LMICs [16,17]. The mammalian cell production platform involves the use of recombinant deoxyribonucleic acid (DNA) technology wherein transgenic mice and cells are produced expressing the mAb gene [15,18]. Approximately 95% of synthesized antibodies utilized for the treatment of rheumatoid arthritis, Crohns disease and several types of malignancy are produced in mammalian cells despite the high production costs, biosafety issues and high investment capital needed [19]. Thus, the development of cost-effective and scalable production platforms that can be very easily implemented in LMICs is usually a necessity. The utilization of molecular farming for the development of mAbs is gaining immense desire for the biopharmaceutical field, Apatinib since this production method is usually significantly safer and more economical when compared to other platforms [8]. is usually a common herb species utilized for the transient and stable expression of mAbs.