**4. Therapeutic potential of** *Trichinella spiralis*

#### **4.1 Therapeutic potential on cancer**

In 1970, Weatherly and collaborators [26] conducted one of the first studies where the therapeutic potential of *T. spiralis* was assessed. The authors observed that parasitized mice survived for longer according to the dose of parasites administered, as well

as having a decrease in breast tumor size compared to non-parasitized mice. Since then, many aspects of the inhibitory effect of *T. spiralis* on cancer have been studied and described, both in animal and *in vitro* models with promising results, ranging from the induction of apoptosis in cancer cells to the total or partial inhibition of the growth of some of the tumors studied. The increase in the survival rate of subjects has also been observed *in vivo* in different experimental models, such as in mice that have been parasitized with ML and inoculated with sarcoma 180 tumor cells, where the suppressive effects on cancer development were observed [27–29]. Inhibition of tumor cell growth has also been observed in experimentally infected mice and rats; the inhibition of the development of B16 melanoma, mammary gland cancer, and the number of histiocytomas appears to be directly proportional to the dose of infection [30–34]. The antitumor effects of *T. spiralis* ML have been tested in BALB/c mice with A549 lung cancer, HCT-8 human colorectal carcinoma and C6 glioma [35–37]. In ICR mice, the mouse esophageal carcinoma and mouse ascitic hepatoma (H22) were studied, while in C57BL/6 mice, the hepatoma by Hepa1–6 carcinoma cells were studied [29, 38, 39]. In all experiments, an inhibitory effect of cancer was reported. In addition, studies have been conducted in mouse models of SP2/0 myeloma and colon cancer also immunized with extracts of the parasite and with their ESPs, which immune- modulate the development of both types of cancer [40–42].

ESPs contain some bioactive substances with known antitumor properties, such as the translationally controlled tumor-protein (TCTP) associated with growth, cell cycle regulation and antiapoptotic and immunomodulatory properties. The presence of caveolin-1 (cav-1), an essential protein component of caveolae that acts as a tumor suppressor, has also been described. Other proteins with antitumor properties are some heat shock proteins (HSPS), such as sHSP, HSP60, HSP70, and H3 and H2B histones, involved in fold stability, intracellular arrangement, and proteolytic turnover of many key regulators of growth, differentiation, and survival; they are vital to prevent cell death and maintain homeostasis in *T. spiralis* [20]. The antitumor properties of ESP and ML extracts were also studied in *in vitro* models of esophageal carcinoma, sarcoma 180, chronic myeloid leukemia, hepatomas, lung cancer, B16 melanoma, human cervical carcinoma, and Graffi myeloid tumor. The incubation of cell cultures with ESP or parasite extract showed results that ranged from tumor apoptosis to inhibitory effect on the proliferation of carcinogenic cells [29, 33, 43–47]. These reports are detailed in **Table 1**.

#### **4.2 Therapeutic potential in autoimmune and allergic diseases**

Currently, more than 80 autoimmune diseases have been described, such as rheumatoid arthritis, systemic lupus erythematosus (SLE), and type I diabetes. Autoimmune diseases affect between 5 and 9% of the world's population and arise from the loss of immune tolerance to self-antigens. Loss of immune tolerance leads to the development of autoreactive T and B cells and the attack of the body's own tissues; for example, an organ-specific attack is presented in rheumatoid arthritis where the target organ is the joints, or it can occur systemically as is the case in SLE [48]. Because *T. spiralis* can induce a Th2-type response in its host to limit the inflammation within the tissue where it is, many studies are focused on the search for new therapies for autoimmune diseases based on these properties. The same happens for allergic diseases, where *T. spiralis* and its ESPs have also shown encouraging results. That is the case of some studies conducted in animal models of allergic asthma, a chronic inflammatory disorder of the respiratory tract with a strong relationship with an exacerbated Th2 response [49].

