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

Abstract

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.

A novel enemy of cancer: recent investigations into protozoan anti-tumor properties

“…demonstrated that mice immunized with autoclaved Toxoplasma vaccine (ATV) produced 13.3% inhibition of Ehrlich solid carcinoma (ESC) genesis and confirmed the existence of at least four pairs of common antigens between ATV and ESC ( Eissa et al., 2023 ). Subsequent results showed that ATV and cyclophosphamide synergistically exerted a stronger tumor immune response and anti-angiogenesis effect in ESC-bearing mice, indicating that ATV has the potential to be a tumor vaccine or cancer drug adjuvant ( Ismail et al., 2023 ).…”

Trichinella spiralis Larval Extract as a Biological Anti‐Tumor Therapy in a Murine Model of Ehrlich Solid Carcinoma

“…Moreover, several studies have reported the promising antineoplastic activity of some protozoa as they can inhibit the growth of a variety of tumors or prolong the survival of tumor-bearing animals such as Trichomonas vaginalis [5,6], Trypanosoma [7,8], Toxoplasma gondii [9][10][11] and Plasmodium species [12,13]. Also, helminthic parasites have gained a respectable reputation for their anti-tumor properties, such as Echinococcus granulosus [14,15] and Trichinella spiralis (T. spiralis), which can adversely affect tumor growth and extend the host lifespan [4,16,17].…”