Over the past three decades, insect biotechnology has grown significantly and found applications across various scientific disciplines, particularly in medicine and agriculture.
Biotechnological methods are commonly applied to insect cells (ICs), especially those of lepidopteran origin, to produce complex proteins with broad utility. This article explores the role of insect-derived biopharmaceutical products and their advantages.
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Insects as a Source of Medicinal Applications
In many regions, including India, Thailand, China, Africa, and Latin America, certain insects have traditionally been consumed for their nutritional value or due to cultural and religious practices.1
In folk medicine, insect extracts have long been used to treat ailments such as the flu, infections, muscle spasms, and digestive issues. These medicinal properties are often attributed to the insects’ high content of proteins, chitin, vitamins, polyunsaturated fatty acids, minerals, and essential amino acids.2
With a growing global population, there's an increasing demand for sustainable sources of food and medicine. Given their historical use for both nutrition and healing, insects are now being considered promising candidates for eco-friendly drug and food production strategies.
Traditional Chinese Medicine (TCM) recognizes around 77 insect species, including Mylabris spp. (cantharis beetles), caterpillars, wasps, bees, silkworms (Bombyx mori), houseflies (Musca domestica), ants, and grubs for their potential anti-tumor effects.1
In Brazil, for instance, ground ants are added to coffee or sugary juice blends to help treat eye conditions.3 In Indian Ayurvedic medicine, insects such as Periplaneta orientalis, Bombyx mori, Vespa orientalis from the Attapadi hills, and Apis cerana indica have been used to manage anemia, malaria, asthma, rheumatism, and ulcers.4
In addition, antimicrobial peptides derived from arthropods, such as defensins, cecropins, and lysozymes, are promising yet underexplored agents for combating pathogenic infections.5
Insect-derived materials like the silk proteins fibroin and sericin also show potential in biomedical applications, particularly in nano-based drug delivery systems. These proteins are biodegradable, biocompatible, non-toxic, and have low immunogenicity.
In vitro studies have shown that silk-based nanoparticles, when loaded with natural drugs like curcumin, peptides, proteins, or chemotherapeutics, offer significant therapeutic benefits. These carriers may also be used to deliver nucleic-acid-based therapies, such as microRNAs (miRNAs), small interfering RNAs (siRNAs), and antisense oligodeoxynucleotides (ASOs).
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Insect Cell Line Development for Medicinal Purposes
Insect cells provide an efficient platform for synthesizing modified eukaryotic proteins in large quantities and shorter timeframes. Beyond protein expression, insect cell cultures are widely used in the production of viral pesticides and vaccines. They also support fundamental research in genetics, virology, morphogenesis, biochemistry, molecular biology, and endocrinology.6
The first insect cell line was established in 1962 by Grace, using ovarian tissues from the Gum Emperor moth (Antheraea eucalypti Scott). Since then, researchers have developed cell lines from insects belonging to several orders, including Hemiptera, Diptera, Coleoptera, Orthoptera, Hymenoptera, Homoptera, and Lepidoptera.7
Among the most commonly used are cell lines derived from the armyworm Spodoptera frugiperda, such as Sf21 and its variant Sf9. These cell lines support replication of Autographa californica nucleopolyhedrovirus (AcMNPV) and are frequently used in vaccine production and protein expression.
Another widely used line derived from Trichoplusia ni embryos is BTI-Tn5B1-4, commercially known as High Five. This line is highly susceptible to AcMNPV and enables high-yield recombinant protein production.8
ESF 921 is a culture medium designed for the insect cell baculovirus expression vector system (IC-BEV) technology. It enhances recombinant protein expression, especially glycosylated proteins, and is extensively used to produce foreign peptides and immunogens.9
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Commercial Applications and Clinical Trials
The BTI-Tn5B1-4 and Sf9 cell lines are at the forefront of virus-like particle (VLP) production, a key element in vaccine development. VLPs mimic the structure of viruses but lack viral genetic material, making them safer and more cost-effective alternatives.6
Several human vaccines and immunotherapeutics developed using Sf21, Sf9, and High Five cells are currently undergoing clinical trials. Some have already reached commercial availability. For example, Provenge, developed by Dendreon (USA) using S. frugiperda cells, is used to treat prostate cancer.
Protein Sciences Inc. (USA) and ViRexx Medical Corp (Canada) have utilized the S. frugiperda system to produce Flublok (for influenza) and Chimigen (for chronic hepatitis B), respectively.
Favrille Inc., a San Diego-based biopharmaceutical company, used High Five cells to develop FavId, an immunotherapeutic vaccine targeting B-cell non-Hodgkin’s lymphoma. Additionally, MedImmune (USA) and GlaxoSmithKline (Belgium) jointly developed Cervarix, a cervical cancer vaccine, using the same cell line.
Gene therapy is also gaining ground as a treatment option for various immune deficiencies and cancers. Baculovirus (BV)-mediated gene transfer has shown strong results in both ex vivo and in vivo studies.10 For instance, recombinant adeno-associated virus (rAAV) vectors developed in Sf9 lepidopteran cells are being tested for gene therapy applications, including targeted approaches for glioma.
Many biotechnology start-ups are leveraging BEVS (baculovirus expression vector system) for the development and commercial production of medicinal and agricultural products. The system’s advantages, fast turnaround times and low costs, make it particularly attractive for manufacturing recombinant proteins and vaccines. Notably, BEVS technology was recently used to produce approximately 1,700 doses of an experimental avian influenza vaccine.
Despite their potential, insect cell expression systems face limitations, such as challenges in producing large amounts of highly purified antigen. However, further innovation can address these hurdles, expanding their applications in medicine and beyond.
References
- Sinha B, Choudhury Y. Revisiting edible insects as sources of therapeutics and drug delivery systems for cancer therapy. Front Pharmacol. 2024;15:1345281. doi: 10.3389/fphar.2024.1345281.
- Li M, et al. Edible Insects: A New Sustainable Nutritional Resource Worth Promoting. Foods. 2023;12(22):4073. doi: 10.3390/foods12224073.
- Siddiqui SA, et al. Unravelling the potential of insects for medicinal purposes - A comprehensive review. Heliyon. 2023;9(5):e15938. doi: 10.1016/j.heliyon.2023.e15938.
- Devi WD, et al. Edible insects: As traditional medicine for human wellness. Future Foods. 2023; 7,100219. doi.org/10.1016/j.fufo.2023.100219
- Duwadi D, et al. Identification and screening of potent antimicrobial peptides in arthropod genomes. Peptides. 2018;103:26-30. doi: 10.1016/j.peptides.2018.01.017.
- Ejiofor AO. Insect Biotechnology. Short Views on Insect Genomics and Proteomics. 2015;4:185–210. doi: 10.1007/978-3-319-24244-6_8.
- He X, et al. Insect Cell-Based Models: Cell Line Establishment and Application in Insecticide Screening and Toxicology Research. Insects. 2023;14(2):104. doi: 10.3390/insects14020104.
- Shan M, et al. Susceptibility to AcMNPV and expression of recombinant proteins by a novel cell clone derived from a Trichoplusia ni QAU-BTI-Tn9-4s cell line. Virol Sin. 2011;26(5):297-305. doi: 10.1007/s12250-011-3201-1.
- Hong M, et al. Genetic engineering of baculovirus-insect cell system to improve protein production. Front Bioeng Biotechnol. 2022;10:994743. doi: 10.3389/fbioe.2022.994743.
- Airenne KJ, et al. Baculovirus: an insect-derived vector for diverse gene transfer applications. Mol Ther. 2013;21(4):739-49. doi: 10.1038/mt.2012.286.
Further Reading