Notes

Surprisingly, the protective rates between two sets of nsEP parameters are very different. A high rate of protection from the second live tumor challenge, 100%, has been observed in both mouse breast cancer [48] and rat hepatocellular cancer models [44] after the same 100 nsEP treatment. Does this mean 100 nsEPs are more favorable to induce immune protection than 200 nsEPs? The answer is not clear because 100 nsEPs has eradicated local mouse lung squamous cell cancer (KLN205) but has failed to result in any vaccine-like protection (0/19 protection in our unpublished data). It's very likely that cancer cell types and distinctive tumor microenvironments play a critical role on the induction of immunity following the nsEP tumor ablation.

p = 0.001 for nsEP-200 ns vs. nsEP-100 ns (Chi Square test).

Figure 8. A vaccine-like protection effect after the nsEP treatment. Growth curves of second challenge pancreatic tumors in tumor-free animals after IRE or nsEPs. Primary pancreatic tumors were treated with IRE (IRE), nsEPs with 200 ns, 2 Hz, 30 kV/cm and 600 -1200 pulses (nsEP-200 ns), or nsEPs with 100 ns, 2 Hz, 50 kV/cm and 800 -1200 pulses (nsEP-100 ns). Number of protective mice vs. total number of challenged mice was indicated. p < 0.05 for nsEP-200 ns vs. IRE and

The growth inhibition of local recurring tumors and the second challenging tumors suggests that underlying common immune responses are induced after the nsEP treatment. It's critical to understand the mechanisms causing the differential responses and outcomes between IRE and nsEPs or among various nsEP parameters, so it is possible forresearchers to design more effective therapeutic strategies, such as further optimization of the system or a combination therapy with other immunomodulators. Currently, we are investigating cell death mechanisms, local and systemic immune responses, and the changes of tumor microenvironments following the nsEP tumor ablation.

Two electric pulse-based technologies have been studied to treat pancreatic cancer in a syngeneic mouse pancreatic cancer model. A novel MHIRE system has been developed. This MHIRE system has three functions including controllable tumor heating, impedance monitoring and electric pulse delivery. MH has been demonstrated to decrease the impedance of tumor, to enlarge the tumor ablation zone of IRE ex vivo and to enhance the complete tumor ablation of the IRE treatment in vivo. The MHIRE treatment significantly improves the therapeutic efficacy of the IRE treatment. In contrast to the IRE treatment, nsEP tumor ablation showed distinctive outcomes and potential advantages. If partial ablation occurred after either the IRE or the nsEP treatment, animals treated with nsEPs received survival benefit. If complete local ablation was achieved, animals treated with nsEPs but not with IRE were able to reject secondary tumor

4. Conclusion

124 Advances in Pancreatic Cancer

The data present in the second section have been published in or modified from the journal of Scientific Report (see [27]).
