Nishi Jain 21′
The testing of such monoclonal antibodies frequently happens with multiple cell lines to test for efficacy. (Source: Wikimedia Commons)
Historically, plastic has been filed alongside tobacco, asbestos, and miscellaneous parabens as a carcinogen, or cancer-causing agent. Scientists continue to warn against overexposure to it – a common example of this involves Bisphenol A (BPA). The chemical BPA has been added frequently to plastics and operates as a hormonal disruptor. BPA affects estrogen and progesterone activity within the body by either mimicking the behavior of these hormones or competing against hormones for the receptors, thereby diminishing the impact of the hormones (1). Such dangers have led manufacturers of water-bottles to go BPA-Free.
However, scientists at the Department of Biotechnology at the University of Verona have suggested reversing the popular anti-plastic opinion, at least for particular applications. These scientists have found a way to shape plastic such that it may reverse the effects of cancer rather than cause or exacerbate them. They have investigated these new plastics as a replacement for monoclonal antibodies, a popular treatment for a variety of cancers. Monoclonal antibodies (mAbs, for short) are harvested from immune cells. These immune proteins bind specifically to certain antigens on the surface of other cells. The ability to bind antigens on the cell surface makes mAbs extremely useful for cancer treatment, as cancer lines frequently overexpress one cell surface receptor (to the mAbs, an antigen) quantitatively more than other healthy cells. The mAbs can selectivity target these overexpressed cell receptors on cancer cells and leave healthy cells alone (avoiding the symptoms caused by chemotherapy such as brittle nails and hair loss) (2).
Traditional mAbs are developed through a lengthy process known as hybridoma technology. Hybridomas use rodent B cells (a type of immune cell) as a canvas. Rodents are injected with a specific antigen, such that their B cells express a complementary antibody. After fusing together these rodent B cells with a myeloma cell (a cell line that’s immortal), the mAbs are given the ability to express the antibody continuously (2).
These mAbs are particularly effective for breast cancer. Many breast cancers are either estrogen receptor positive (ER+) or human epidermal growth factor receptor 2 positive (HER2+) and have thousands of each receptor on their cell surface. Treatment of breast cancer is greatly facilitated by having a mAb that focuses on these receptors and targets them selectively. While mAbs can be hugely beneficial, a large problem with their processing is that they always require humanization – a method of adjusting the antibody to make it resemble what people have inside their own cellular systems (3). The humanization process takes a long time and is very costly.
Enter the plastic mAb. Scientists are developing imprinted polymer nanoparticles (also known as MIP-NPs) that can block cadherins, proteins that bind cells together and play a significant role in the proliferation and metastasis of tumors. These MIP-NPs are built with the simple idea that the molecular structure and shape of a target can be imprinted into a template. The complementary structure can then be created and replicated quicker and more efficiently than more pure biological techniques that rebuild the same target structures every time (such as hybridomas). To do this, a molecular template is introduced into the synthetic scheme with a polymer chain such that the chain grows around the template as a complement. The template is then washed away from the mix and leaves only the complementary molecular shape that can effectively bind to the target molecule or antigen (3).
So far, MIPs have shown efficacy within in vitro studies looking at the proliferation and metastatic status of certain HeLa cells in culture (3). Scientists are now looking to further in vivo studies within certain model organisms to try and reproduce these promising results. If found to be similar, this powerful technology could make pre-clinical cancer research significantly more efficient and inexpensive.
References:
[1] Rochester JR. (2013). Bisphenol A and human health: A review of the literature. Reprod. Toxicol., 42, 132–55. https://doi.org/10.1016/j.reprotox.2013.08.008.
[2] Burris III, H. A., Giaccone, G. & Im, S. A. (2015). Updated findings of a first-in-human phase 1 study of margetuximab, an Fc-optimized chimeric monoclonal antibody, in patients with HER2-positive advanced solid tumors [abstract]. Am. Soc. Clin. Oncol. Meet. 33 (no. 15_suppl), A523.
[3] Bossi, A.M. (2020). Plastic antibodies for cancer therapy?. Nat. Chem, 12, 111–112. https://doi.org/10.1038/s41557-019-0415-6