Title

Intratumoral Immunotherapy with NanoPulse Stimulation and anti-PD-L1-Functionalized Carbon Nanotubes in B16f10 Melanoma

Document Type

Presentation

Publication Date

11-11-2021

Speaker Biographical Sketch

Kamal Asadipour

Kamal Asadipour is a graduate research assistant and is pursuing a PhD degree in Biomedical Engineering in the Department of Electrical & Computer Engineering. His research interests include bioelectrics, immunology, biomaterials.

Category

Young Investigator

Session

Bioengineering

Format

Recorded

DOI

10.25776/0wbe-1d16

Conference Name

2021 Frank Reidy Research Center for Bioelectrics Retreat

Abstract

In two well characterized orthotopic rodent tumor models [1-3] NanoPulse Stimulation (NPS) provides an intratumoral immunotherapy by using the tumor as its own vaccine. NPS not only ablates many types of orthotopic and ectopic tumors in rats, mice and humans [4], but also induces immunogenic cell death [1, 5], activates T-cell-dependent immune responses, activates innate immunity, reverses immunosuppression, and can transform tumors into in situ vaccines [3]. However, not all tumor models readily response to NPS with immune induction and in situ vaccination. One of these is the mouseB16f10 melanoma model. To enhance NPS-induced immunity we will include another immunotherapy such as intratumoral delivery of anti- PD-L1 or anti-PD-1. However, immunotherapy requires two phases, a priming phase, and an effector phase [6]. Anti-PD-L1 therapy is believed to begin in the effector phase of immunity. By combining these therapies, NPS would provide the priming phase and anti-PD-L1 would enhance the NPS-induced effector phase. However, low anticancer treatment efficacy might be caused by a limited electric field coverage. A high electric field with a strength of as high as 50 kV/cm has been shown to be effective. Because of clinical consideration, such a high field is concerning. As a result, several additional modalities may be useful because of their high aspect ratio and strong conductivity. Multi-walled carbon nanotubes (MWCNTs), a type of new carbon allotrope, have been discovered to have field emission capability [7]. CNTs can amplify the electric field surrounding their tips due to their unique electronic properties, resulting in a localized high field zone [8]. When CNTs are combined with low-intensity electric pulses, stronger cell electro-responses are achieved [9]. Carbon nanotubes, on the other hand, have been shown to be cancer-targeted via both passive and active pathways, and to have a high level of tumor uptake [10]. Given these promising properties, MWCNTs will be used in combination with lower electric field stimulation to enhance cancer cell death and intratumoral antibody delivery.

We hypothesize that treating B16f10 melanoma cells with intratumoral MWCNT covalently functionalized with mouse PD-L1 antibody (MWCNT-anti-PDL1 or anti-PD-1) in combination with NPS treatment will reduce NPS conditions for efficacy [11], improve electrical safety and activate multiple anti-cancer and pro-immunity mechanisms in B16f10 melanoma. In vitro data with B16f10 melanoma cells indicate that NPS can reduce the lethality requirements for high NPS conditions by 3-5-fold.

Comments

REFERENCES

  1. Guo, S., et al., Nano‐pulse stimulation induces potent immune responses, eradicating local breast cancer while reducing distant metastases. International journal of cancer, 2018. 142(3): p. 629-640.
  2. Lassiter, B.P., S. Guo, and S.J. Beebe, Nano-pulse stimulation ablates orthotopic rat hepatocellular carcinoma and induces innate and adaptive memory immune mechanisms that prevent recurrence. Cancers, 2018. 10(3): p. 69.
  3. Beebe, S.J., B.P. Lassiter, and S. Guo, Nanopulse stimulation (NPS) induces tumor ablation and immunity in orthotopic 4T1 mouse breast cancer: a review. Cancers, 2018. 10(4): p. 97.
  4. Beebe, S.A., S.J. Beebe, and D.K. Ivy, Communication: Principles for a lifetime. 2016: Pearson.
  5. Nuccitelli, R., et al., Nano-Pulse Stimulation is a physical modality that can trigger immunogenic tumor cell death. Journal for immunotherapy of cancer, 2017. 5(1): p. 1-13.
  6. Marabelle, A., et al., Intratumoral immunotherapy: using the tumor as the remedy. Annals of oncology, 2017. 28: p. xii33-xii43.
  7. Li, H.J., et al., Multichannel ballistic transport in multiwall carbon nanotubes. Physical review letters, 2005. 95(8): p. 086601.
  8. Rojas-Chapana, J.A., et al., Enhanced introduction of gold nanoparticles into vital acidothiobacillus ferrooxidans by carbon nanotube-based microwave electroporation. Nano Letters, 2004. 4(5): p. 985-988.
  9. Stacey, M., et al., Nanosecond pulse electrical fields used in conjunction with multi-wall carbon nanotubes as a potential tumor treatment. Biomedical Materials, 2011. 6(1): p. 011002.
  10. Smith, B.R., et al., Selective uptake of single-walled carbon nanotubes by circulating monocytes for enhanced tumour delivery. Nature nanotechnology, 2014. 9(6): p. 481-487.
  11. Mi, Y., et al., Multi-parametric study of the viability of in vitro skin cancer cells exposed to nanosecond pulsed electric fields combined with multi-walled carbon nanotubes. Technology in cancer research & treatment, 2019. 18: p. 1533033819876918.

ORCID

0000-0002-6075-9452 (Beebe)

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