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A Non-Invasive Deep Photoablation Technique to Inhibit DCIS Progression and Induce Antitumor Immunity.

Publication ,  Journal Article
Kaneko, K; Nagata, H; Yang, X-Y; Ginzel, J; Hartman, Z; Everitt, J; Hughes, P; Haystead, T; Morse, M; Lyerly, HK; Osada, T
Published in: Cancers (Basel)
November 23, 2022

Ductal carcinoma in situ (DCIS) of the breast is often managed by lumpectomy and radiation or mastectomy, despite its indolent features. Effective non-invasive treatment strategies could reduce the morbidity of DCIS treatment. We have exploited the high heat shock protein 90 (HSP90) activity in premalignant and malignant breast disease to non-invasively detect and selectively ablate tumors using photodynamic therapy (PDT). PDT with the HSP90-targeting photosensitizer, HS201, can not only ablate invasive breast cancers (BCs) while sparing non-tumor tissue, but also induce antitumor immunity. We hypothesized that HS201-PDT would both non-invasively ablate DCIS and prevent progression to invasive BC. We tested in vitro selective uptake and photosensitivity of HS201 in DCIS cell lines compared to the non-selective parental verteporfin, and assessed in vivo antitumor efficacy in mammary fat pad and intraductal implantation models. Selective uptake of HS201 enabled treatment of intraductal lesions while minimizing toxicity to non-tumor tissue. The in vivo activity of HS201-PDT was also tested in female MMTV-neu mice prior to the development of spontaneous invasive BC. Mice aged 5 months were administered HS201, and their mammary glands were exposed to laser light. HS201-PDT delayed the emergence of invasive BC, significantly prolonged disease-free survival (DFS) (p = 0.0328) and tended to improve overall survival compared to the no-treatment control (p = 0.0872). Systemic administration of anti-PD-L1 was combined with HS201-PDT and was tested in a more aggressive spontaneous tumor model, HER2delta16 transgenic mice. A single PDT dose combined with anti-PD-L1 improved DFS compared to the no-treatment control, which was significantly improved with repetitive HS201-PDT given with anti-PD-L1 (p = 0.0319). In conclusion, a non-invasive, skin- and tissue-sparing PDT strategy in combination with anti-PD-L1 antibodies effectively prevented malignant progression of DCIS to invasive BC. This non-invasive treatment strategy of DCIS may be safe and effective, while providing an option to reduce the morbidity of current conventional treatment for patients with DCIS. Clinical testing of HS201 is currently underway.

Duke Scholars

Published In

Cancers (Basel)

DOI

ISSN

2072-6694

Publication Date

November 23, 2022

Volume

14

Issue

23

Location

Switzerland

Related Subject Headings

  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kaneko, K., Nagata, H., Yang, X.-Y., Ginzel, J., Hartman, Z., Everitt, J., … Osada, T. (2022). A Non-Invasive Deep Photoablation Technique to Inhibit DCIS Progression and Induce Antitumor Immunity. Cancers (Basel), 14(23). https://doi.org/10.3390/cancers14235762
Kaneko, Kensuke, Hiroshi Nagata, Xiao-Yi Yang, Joshua Ginzel, Zachary Hartman, Jeffrey Everitt, Philip Hughes, et al. “A Non-Invasive Deep Photoablation Technique to Inhibit DCIS Progression and Induce Antitumor Immunity.Cancers (Basel) 14, no. 23 (November 23, 2022). https://doi.org/10.3390/cancers14235762.
Kaneko K, Nagata H, Yang X-Y, Ginzel J, Hartman Z, Everitt J, et al. A Non-Invasive Deep Photoablation Technique to Inhibit DCIS Progression and Induce Antitumor Immunity. Cancers (Basel). 2022 Nov 23;14(23).
Kaneko, Kensuke, et al. “A Non-Invasive Deep Photoablation Technique to Inhibit DCIS Progression and Induce Antitumor Immunity.Cancers (Basel), vol. 14, no. 23, Nov. 2022. Pubmed, doi:10.3390/cancers14235762.
Kaneko K, Nagata H, Yang X-Y, Ginzel J, Hartman Z, Everitt J, Hughes P, Haystead T, Morse M, Lyerly HK, Osada T. A Non-Invasive Deep Photoablation Technique to Inhibit DCIS Progression and Induce Antitumor Immunity. Cancers (Basel). 2022 Nov 23;14(23).

Published In

Cancers (Basel)

DOI

ISSN

2072-6694

Publication Date

November 23, 2022

Volume

14

Issue

23

Location

Switzerland

Related Subject Headings

  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis