Abstract
Establishment of an in vivo small animal model of human tumor and human immune system interaction would enable preclinical investigations into themechanisms underlying cancer immunotherapy. To this end, nonobese diabetic (NOD).Cg-PrkdcscidIL2rgtm1Wjl/Sz (null; NSG) mice were transplanted with human (h)CD34+ hematopoietic progenitor and stem cells, which leads to the development of human hematopoietic and immune systems [humanized NSG (HuNSG)]. HuNSG mice received human leukocyte antigen partially matched tumor implants from patientderived xenografts [PDX;non-small cell lungcancer (NSCLC), sarcoma, bladder cancer, andtriple-negative breast cancer (TNBC)] or from a TNBC cell line-derived xenograft (CDX). Tumor growth curves were similar in HuNSG compared with nonhuman immune-engrafted NSGmice. Treatmentwith pembrolizumab, which targets programmed cell death protein 1, produced significant growth inhibition inbothCDXandPDXtumorsinHuNSGbut not inNSGmice. Finally, inhibition of tumor growth was dependent on hCD8+ T cells, as demonstrated by antibody-mediated depletion. Thus, tumor-bearingHuNSG mice may represent an important, newmodel for preclinical immunotherapy research.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1537-1549 |
| Number of pages | 13 |
| Journal | FASEB Journal |
| Volume | 32 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 1 2018 |
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Keywords
- Checkpoint inhibitor
- Mouse model
- Patient-derived xenograft
- Pembrolizumab
ASJC Scopus subject areas
- Biotechnology
- Biochemistry
- Molecular Biology
- Genetics
Cite this
Humanized mice in studying efficacy and mechanisms of PD-1-targeted cancer immunotherapy. / Wang, Minan; Yao, Li Chin; Cheng, Mingshan; Cai, Danying; Martinek, Jan; Pan, Chong-Xian; Shi, Wei; Ma, Ai Hong; deVere White, Ralph W; Airhart, Susan; Liu, Edison T.; Banchereau, Jacques; Brehm, Michael A.; Greiner, Dale L.; Shultz, Leonard D.; Palucka, Karolina; Keck, James G.
In: FASEB Journal, Vol. 32, No. 3, 01.03.2018, p. 1537-1549.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Humanized mice in studying efficacy and mechanisms of PD-1-targeted cancer immunotherapy
AU - Wang, Minan
AU - Yao, Li Chin
AU - Cheng, Mingshan
AU - Cai, Danying
AU - Martinek, Jan
AU - Pan, Chong-Xian
AU - Shi, Wei
AU - Ma, Ai Hong
AU - deVere White, Ralph W
AU - Airhart, Susan
AU - Liu, Edison T.
AU - Banchereau, Jacques
AU - Brehm, Michael A.
AU - Greiner, Dale L.
AU - Shultz, Leonard D.
AU - Palucka, Karolina
AU - Keck, James G.
PY - 2018/3/1
Y1 - 2018/3/1
N2 - Establishment of an in vivo small animal model of human tumor and human immune system interaction would enable preclinical investigations into themechanisms underlying cancer immunotherapy. To this end, nonobese diabetic (NOD).Cg-PrkdcscidIL2rgtm1Wjl/Sz (null; NSG) mice were transplanted with human (h)CD34+ hematopoietic progenitor and stem cells, which leads to the development of human hematopoietic and immune systems [humanized NSG (HuNSG)]. HuNSG mice received human leukocyte antigen partially matched tumor implants from patientderived xenografts [PDX;non-small cell lungcancer (NSCLC), sarcoma, bladder cancer, andtriple-negative breast cancer (TNBC)] or from a TNBC cell line-derived xenograft (CDX). Tumor growth curves were similar in HuNSG compared with nonhuman immune-engrafted NSGmice. Treatmentwith pembrolizumab, which targets programmed cell death protein 1, produced significant growth inhibition inbothCDXandPDXtumorsinHuNSGbut not inNSGmice. Finally, inhibition of tumor growth was dependent on hCD8+ T cells, as demonstrated by antibody-mediated depletion. Thus, tumor-bearingHuNSG mice may represent an important, newmodel for preclinical immunotherapy research.
AB - Establishment of an in vivo small animal model of human tumor and human immune system interaction would enable preclinical investigations into themechanisms underlying cancer immunotherapy. To this end, nonobese diabetic (NOD).Cg-PrkdcscidIL2rgtm1Wjl/Sz (null; NSG) mice were transplanted with human (h)CD34+ hematopoietic progenitor and stem cells, which leads to the development of human hematopoietic and immune systems [humanized NSG (HuNSG)]. HuNSG mice received human leukocyte antigen partially matched tumor implants from patientderived xenografts [PDX;non-small cell lungcancer (NSCLC), sarcoma, bladder cancer, andtriple-negative breast cancer (TNBC)] or from a TNBC cell line-derived xenograft (CDX). Tumor growth curves were similar in HuNSG compared with nonhuman immune-engrafted NSGmice. Treatmentwith pembrolizumab, which targets programmed cell death protein 1, produced significant growth inhibition inbothCDXandPDXtumorsinHuNSGbut not inNSGmice. Finally, inhibition of tumor growth was dependent on hCD8+ T cells, as demonstrated by antibody-mediated depletion. Thus, tumor-bearingHuNSG mice may represent an important, newmodel for preclinical immunotherapy research.
KW - Checkpoint inhibitor
KW - Mouse model
KW - Patient-derived xenograft
KW - Pembrolizumab
UR - http://www.scopus.com/inward/record.url?scp=85043580332&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85043580332&partnerID=8YFLogxK
U2 - 10.1096/fj.201700740R
DO - 10.1096/fj.201700740R
M3 - Article
C2 - 29146734
AN - SCOPUS:85043580332
VL - 32
SP - 1537
EP - 1549
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 3
ER -