76P - Improvement of whole-cell cancer vaccine anti-tumor effect by different injection methods

Background

It is common for cancer to recur even after successful treatment of the primary tumor. Recurrent or metastatic cancers are less responsive to existing therapies and often have high mortality rate. Whole-cell cancer vaccine, which utilizes patient-derived primary tumor tissue may be a promising approach in preventing recurrence. A major advantage is the provision of a plethora of patient-specific tumor antigens, but overall whole-cell vaccine efficacy is still limited and insufficient. To improve on the efficacy of whole-cell cancer vaccine, we explored the use of different injection methods. It has been previously shown that injection method and location of injection may vary vaccine efficacy and effects. Therefore, we investigated different injection methods to improve the effectiveness of the whole-cell cancer vaccine.

Methods

We compared the efficacy of needle-syringe injection and needle-free (pyro-drive jet injector) injection to evaluate the differences in effectiveness of whole-cell cancer vaccines using murine MC38 colon adenocarcinoma or 4T1 mammary tumor cell lines, by analyzing tumor challenge and the inhibition of cancer metastasis using the C57BL/6 and BALB/c mouse models. We also analyzed the in vitro activation of APCs and innate immune cells using the expelled whole-cell vaccine following each injection method by flow cytometry, cytokine array and quantitative real-time PCR.

Results

Our results showed that whole-cell vaccine administered via needle-free injection induced higher tumor suppression effect and stronger tumor-specific immunity than traditional needle-syringe injection in both MC38 and 4T1 tumor models. In vitro, the whole-cell cancer vaccine preparation discharged through the needle-free injection device induced a stronger immune stimulation on immune cells than from the syringe method.

Conclusions

In contrast to needle injection, needle-free injection of whole-cell cancer vaccine resulted in more pulverized cancer cell fragments, which potentiates APC phagocytosis and adaptive immune activation, thereby improving anti-tumor effect of the vaccine. Therefore, needle-free injection or pre-pulverized formulations should be considered to improve anti-tumor effects of whole-cell cancer vaccines.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Osaka University.

Funding

Japanese Government KAKEN Grants.

Disclosure

All authors have declared no conflicts of interest.