Abstract
Focal ablative therapies have been primarily used for local tumor ablation. However, they often fail to impact systemic disease. Here we propose the use of low intensity focused ultrasound (LOFU), a noninvasive, nontoxic, conformal therapy, to deliver acoustic stress to the tumor for immune priming. We demonstrate that LOFU significantly induces expression and cell surface localization of heat shock proteins in murine breast (4T1) and prostate adenocarcinoma (TPSA23) cancer cell lines. In vivo LOFU followed by ablative radiation therapy (RT) results in primary tumor cure, upregulation of a cytotoxic immune response and induction of immunological memory by inhibiting secondary tumor growth upon re-challenge with tumor cells. We, therefore, describe a regimen of a combination therapy with noninvasive, acoustic immune priming and ablative radiation therapy to generate an in situ tumor vaccine, induce CD8+ T cells against tumor-associated antigens and provide a viable oncologic treatment option for solid tumors.
| Original language | English (US) |
|---|---|
| Article number | 15516 |
| Journal | Scientific Reports |
| Volume | 9 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 1 2019 |
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- General
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Low Intensity Focused Ultrasound (LOFU)-mediated Acoustic Immune Priming and Ablative Radiation Therapy for in situ Tumor Vaccines. / Skalina, Karin A.; Singh, Saurabh; Chavez, Claudia Gutierrez; Macian, Fernando; Guha, Chandan.
In: Scientific Reports, Vol. 9, No. 1, 15516, 01.12.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Low Intensity Focused Ultrasound (LOFU)-mediated Acoustic Immune Priming and Ablative Radiation Therapy for in situ Tumor Vaccines
AU - Skalina, Karin A.
AU - Singh, Saurabh
AU - Chavez, Claudia Gutierrez
AU - Macian, Fernando
AU - Guha, Chandan
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Focal ablative therapies have been primarily used for local tumor ablation. However, they often fail to impact systemic disease. Here we propose the use of low intensity focused ultrasound (LOFU), a noninvasive, nontoxic, conformal therapy, to deliver acoustic stress to the tumor for immune priming. We demonstrate that LOFU significantly induces expression and cell surface localization of heat shock proteins in murine breast (4T1) and prostate adenocarcinoma (TPSA23) cancer cell lines. In vivo LOFU followed by ablative radiation therapy (RT) results in primary tumor cure, upregulation of a cytotoxic immune response and induction of immunological memory by inhibiting secondary tumor growth upon re-challenge with tumor cells. We, therefore, describe a regimen of a combination therapy with noninvasive, acoustic immune priming and ablative radiation therapy to generate an in situ tumor vaccine, induce CD8+ T cells against tumor-associated antigens and provide a viable oncologic treatment option for solid tumors.
AB - Focal ablative therapies have been primarily used for local tumor ablation. However, they often fail to impact systemic disease. Here we propose the use of low intensity focused ultrasound (LOFU), a noninvasive, nontoxic, conformal therapy, to deliver acoustic stress to the tumor for immune priming. We demonstrate that LOFU significantly induces expression and cell surface localization of heat shock proteins in murine breast (4T1) and prostate adenocarcinoma (TPSA23) cancer cell lines. In vivo LOFU followed by ablative radiation therapy (RT) results in primary tumor cure, upregulation of a cytotoxic immune response and induction of immunological memory by inhibiting secondary tumor growth upon re-challenge with tumor cells. We, therefore, describe a regimen of a combination therapy with noninvasive, acoustic immune priming and ablative radiation therapy to generate an in situ tumor vaccine, induce CD8+ T cells against tumor-associated antigens and provide a viable oncologic treatment option for solid tumors.
UR - http://www.scopus.com/inward/record.url?scp=85074287477&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85074287477&partnerID=8YFLogxK
U2 - 10.1038/s41598-019-51332-4
DO - 10.1038/s41598-019-51332-4
M3 - Article
C2 - 31664044
AN - SCOPUS:85074287477
VL - 9
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 15516
ER -