Parasites revive hope for cancer therapy.

Parasites have attained a life-long stigma of being detrimental organisms with deleterious outcomes. Yet, recently, a creditable twist was verified that can dramatically change our perception of those parasites from being a source of misery to millions of people to a useful anti-cancerous tool. Various parasites have shown promise to combat cancer in different experimental models, including colorectal, lung, and breast cancers, among others. Helminths and protozoan parasites, as well as their derivatives such as Echinococcus granulosus protein KI-1, Toxoplasma gondii GRA15II, and Trypanosoma cruzi calreticulin, have demonstrated the ability to inhibit tumor growth, angiogenesis, and metastasis. This article provides an overview of the literature on various cancer types that have shown promising responses to parasite therapy in both in vitro and in vivo animal studies. Parasites have shown anti-neoplastic activity through a variety of mechanisms that collectively contribute to their anti-cancer properties. These include immunomodulation, inhibition of angiogenesis, and molecular mimicry with cancer cells. This review article sheds light on this intriguing emerging field and emphasizes the value of collaborative multidisciplinary research projects with funding agencies and pharmaceutical companies. Thus, these strategies would secure continuous exploration of this new avenue and accelerate the advancement of cancer therapy research. Although experimental studies are heavily conducted by leaps and bounds, further steps are definitely lagging. Upgrading research from the experimental level to the clinical trial would be a wise progression toward efficient exploitation of the anti-neoplastic capabilities of parasites, ultimately saving countless lives.

Shedding light on a mysterious link between Toxoplasma gondii and cancer: A review.

The ongoing conflict regarding the affiliation of Toxoplasma gondii to cancer; whether an inducer or a suppressor needs to be resolved. Human epidemiological studies oscillate without attaining a firm ground. Some studies confirmed the detection of high seroprevalence of anti-Toxoplasma antibodies in different cancer patients without further justification whether being causation, co-incidences, or part of opportunistic infections. Others reported a state of resistance to cancer accompanying low titer of anti-Toxoplasma antibody. Worthwhile, preclinical experimental work confirmed the antineoplastic potency of Toxoplasma. Thus, further investigational research is essential to validate the potential application of Toxoplasma as a promising cancer immunotherapeutic vaccine candidate. In this paper, we present a review of this issue by examining epidemiological and preclinical experimental studies that explored the linkage between Toxoplasma gondii and cancer. We consider this review an important step towards shedding a light on this mysterious link and a stepping-stone for potential research work addressing Toxoplasma as a cancer suppressor rather than a cancer inducer.

Prophylactic antineoplastic activity of Toxoplasma gondii RH derived antigen against ehrlich solid carcinoma with evidence of shared antigens by comparative immunoblotting.

BACKGROUND: With cancer cases escalation, an urgent request to develop novel combating strategies arise. Pathogen-based cancer-immunotherapy is getting more consideration. Autoclaved parasitic antigens seem promising candidates, taking steadily their first steps. Our aim was to examine the prophylactic antineoplastic activity of autoclaved Toxoplasma vaccine (ATV) and to test for the shared antigen theory between Toxoplasma gondii and cancer cells. METHODS: Mice were immunized with ATV followed by Ehrlich solid carcinoma (ESC) inoculation. Tumor weight, volume, histopathology, and immunohistochemistry for CD8+ T cells, Treg cells and VEGF were assessed. In addition, the proposed shared antigen theory between parasites and cancer was also verified using SDS-PAGE and immunoblotting. RESULTS: Results revealed powerful prophylactic activity of ATV with 13.3% inhibition of ESC incidence, significant reduction in tumor weight and volume in ATV vaccinated mice. Immunologically, significantly higher CD8+T cells and lower FOXP3+ Treg cells surrounded and infiltrated ESC in ATV immunized mice with higher CD8+T/Treg cells ratio and significant antiangiogenic effect. Moreover, SDS-PAGE and immunoblotting showed four shared bands between Ehrlich carcinoma and ATV of approximate molecular weights 60, 26, 22 and 12.5 KDa. CONCLUSION: Exclusively, we demonstrated a prophylactic antineoplastic activity of autoclaved Toxoplasma vaccine against ESC. Moreover, to the best of our knowledge this is the first report highlighting the existence of cross-reactive antigens between Toxoplasma gondi parasite and cancer cells of Ehrlich carcinoma.

Toxoplasma gondii-derived antigen modifies tumor microenvironment of Ehrlich solid carcinoma murine model and enhances immunotherapeutic activity of cyclophosphamide.

Pathogen-based cancer vaccine is a promising immunotherapeutic weapon to stimulate cancer immunosuppressive state. Toxoplasma gondii is a potent immunostimulant, and low-dose infection was linked to cancer resistance. Our goal was to evaluate the therapeutic antineoplastic activity of autoclaved Toxoplasma vaccine (ATV) against Ehrlich solid carcinoma (ESC) in mice in reference to and in combination with low-dose cyclophosphamide (CP), a cancer immunomodulator. Mice inoculation with ESC was followed by applying different treatment modalities including ATV, CP, and CP/ATV. We evaluated the impact of the different treatments on liver enzymes and pathology, tumor weight, volume, and histopathological changes. Using immunohistochemistry, we evaluated CD8+ T cell, FOXP3+ Treg, CD8+/Treg outside and inside ESC, and angiogenesis. Results showed significant tumor weights and volumes reduction with all treatments with 13.3% inhibition of tumor development upon combined CP/ATV use. Significant necrosis and fibrosis were noted in ESC by all treatments with improved hepatic functions versus non-treated control. Although ATV was almost equivalent to CP in tumor gross and histopathology, it promoted an immunostimulatory activity with significant Treg cells depletion outside ESC and CD8+ T cells infiltration inside ESC with higher CD8+ T/Treg ratio inside ESC superior to CP. Combined with CP, ATV exhibited significant synergistic immunotherapeutic and antiangiogenic action compared to either treatment alone with significant Kupffer cells hyperplasia and hypertrophy. Exclusively, therapeutic antineoplastic and antiangiogenic activity of ATV against ESC was verified that boosted CP immunomodulatory action which highlights a novel biological cancer immunotherapeutic vaccine candidate.

Multilocus sequencing of Hepatozoon cf. griseisciuri infections in Ontario eastern gray squirrels (Sciurus carolinensis) uncovers two genotypically distinct sympatric parasite species.

Intra-leukocytic gamonts consistent with the description of Hepatozoon griseisciuri Clark, 1958 are reported for the first time in Canadian eastern gray squirrels (Sciurus carolinensis Gmelin, 1788). Polymerase chain reaction (PCR) amplification and direct Sanger sequencing identified a pair of distinct genotypes at both a nuclear and mitochondrial locus; two 18S ribosomal RNA gene sequences (rDNA; genotype A and genotype B: 1816 base pairs (bp); 98.8% pairwise identity) and 2 distinct complete mitochondrial genome sequences (genotype A: 6311 bp; genotype B: 6114 bp; 89.1% pairwise identity) were obtained from 3 H. griseisciuri-infected squirrels sampled in Guelph, Ontario. The genetic content of both circular-mapping mitochondrial genomes was conventional for apicomplexan protists; each encoded for 3 protein-coding genes (cytochrome c oxidase subunit I (COI); cytochrome c oxidase subunit III (COIII); and cytochrome B (CytB)), 14 fragmented large subunit rDNA, 10 fragmented small subunit rDNA, and 8 unassigned rDNA. These genotypes, based on sequences obtained from a pair of loci from two parasite genomes, confirm the presence of at least two Hepatozoon species infecting Ontario eastern gray squirrels, one of which is likely to be conspecific with H. griseisciuri.