Bacterial ghosts as adjuvants in syngeneic tumour cell lysate-based anticancer vaccination in a murine lung carcinoma model

Abstract

Instead of relying on external anticancer factors for treatment, immunotherapy utilizes the host's own immune system and directs it against given tumour antigens. This study demonstrated that it is possible to overcome the documented immunosuppressive properties of tumour cell lysate by supplementing it with appropriate adjuvant. Lewis lung carcinoma (LLC)‑challenged C57BL/6 mice were treated with LLC cryo‑lysate mixed with either bacterial ghosts (BGs) generated from E. coli Nissle 1917 or B. subtilis 70 kDa protein as adjuvants. Median and overall survival, the size of metastatic foci in lung tissue and levels of circulating CD8a+ T cells were evaluated and compared to the untreated control mice or mice treated with LLC lysate alone. After primary tumour removal, a course of three subcutaneous vaccinations with LLC lysate supplemented with BGs led to a significant increase in overall survival (80% after 84 days of follow‑up vs. 40% in untreated control mice), a significant increase in circulating CD8a+ T cells (16.57 vs. 12.6% in untreated control mice) and a significant decrease in metastasis foci area and incidence. LLC lysate supplemented with B. subtilis protein also improved the inspected parameters in the treated mice, when compared against the untreated control mice, but not to a significant degree. Therefore, whole cell lysate supplemented with BGs emerges as an immunostimulatory construct with potential clinical applications in cancer treatment.

Post-operative unadjuvanted therapeutic xenovaccination with chicken whole embryo vaccine suppresses distant micrometastases and prolongs survival in a murine Lewis lung carcinoma model

“…This was a larger percentage compared with the value reported in a previous study (39), where a value of 16.6% CD8 + T lymphocytes was reported for an autologous lysate-based vaccine, which was considered to be clinically successful. The strong statistical correlation between the mean survival time and CD8a + population size in the present study (r= 0.985) indicates that cytotoxic T-lymphocytes may be a pivotal element in the vaccine-induced antitumour immune response, which is in agreement with data from the literature (40)(41)(42)(43)(44).…”

“…In a previously investigated metastatic LLC model, where B. subtilis was used as an adjuvant for an autologous tumour lysate-based vaccine, it failed to demonstrate satisfactory clinical benefits (39); an underperformance repeated in the present study. It is well established that the choice of an appropriate vaccine adjuvant is of critical importance, since inappropriate adjuvants may not only lack its desired activity, but also trigger tolerogenic immune response (53).…”

“…We hypothesize that, for the xeno rat vaccine, the cross-reactivity between the vaccine proteins and LLC antigens is inadequate, likely to be due to insufficient protein homology. In addition, distinct spectrum of TAAs in B16 melanoma and LCC lung cancer cells may be responsible for the xeno rat vaccine exhibiting (39), and this underperformance was repeated in the present study. Various vaccines (preventive and therapeutic) are generally used with vaccine adjuvants that shape and potentiate the induced immune responses, thereby increasing the efficacy of vaccination (45,46).…”

Bioengineered Escherichia coli Nissle 1917 for tumour‐targeting therapy

“…Due to the external immunologic properties of living bacteria, EcN BGs were used as candidate adjuvants. This was done by cell lysate‐based anticancer vaccination of a syngeneic murine lung carcinoma model (Kraśko et al , ). These results indicate that EcN BGs are a promising drug delivery carrier for drug candidates in cancer therapy.…”

“…The combination of EcN‐derived minicells with ligands against tumour‐associated markers has additional tumour‐targeting effects (Zhang et al , ). EcN BGs exhibit excellent immunogenicity and can be used as candidate adjuvants for anticancer vaccination (Kraśko et al , ). The choice of a suitable delivery system (EcN, EcN‐derived minicells or BGs shown in Fig.…”