Abstract
KRAS mutant non-small-cell lung cancer (NSCLC) remains refractory to targeted therapeutics. Choi et al. show that pulsatile, rather than continuous, treatment with MEK inhibitors can maintain T cell activity better and prolong survival in mice with Kras mutant cancer. This effect is further enhanced when combined with CTLA-4 blockade.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 806-819.e5 |
| Journal | Cell Reports |
| Volume | 27 |
| Issue number | 3 |
| DOIs | |
| State | Published - Apr 16 2019 |
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Fingerprint
Dive into the research topics of 'Pulsatile MEK Inhibition Improves Anti-tumor Immunity and T Cell Function in Murine Kras Mutant Lung Cancer'. Together they form a unique fingerprint.Cite this
- APA
- Standard
- Harvard
- Vancouver
- Author
- BIBTEX
- RIS
In: Cell Reports, Vol. 27, No. 3, 16.04.2019, p. 806-819.e5.
Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Pulsatile MEK Inhibition Improves Anti-tumor Immunity and T Cell Function in Murine Kras Mutant Lung Cancer
AU - Choi, Hyejin
AU - Deng, Jiehui
AU - Li, Shuai
AU - Silk, Tarik
AU - Dong, Lauren
AU - Brea, Elliott J.
AU - Houghton, Sean
AU - Redmond, David
AU - Zhong, Hong
AU - Boiarsky, Jonathan
AU - Akbay, Esra A.
AU - Smith, Paul D.
AU - Merghoub, Taha
AU - Wong, Kwok Kin
AU - Wolchok, Jedd D.
N1 - Funding Information: We thank Nouraiz Falik for the work on validation animal experiments. This research was funded in part through a Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant ( SU2C-AACR-DT17-15 ); NIH-NCI Cancer Center Support grant P30 CA008748 ; the Ludwig Collaborative and Swim Across America Laboratory ; Memorial Sloan Kettering Cancer Center , United States; the Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center ; the Department of Medicine, Memorial Sloan Kettering Cancer Center ; and Weill Cornell Medicine , United States. Funding Information: We thank Nouraiz Falik for the work on validation animal experiments. This research was funded in part through a Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant (SU2C-AACR-DT17-15); NIH-NCI Cancer Center Support grant P30 CA008748; the Ludwig Collaborative and Swim Across America Laboratory; Memorial Sloan Kettering Cancer Center, United States; the Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center; the Department of Medicine, Memorial Sloan Kettering Cancer Center; and Weill Cornell Medicine, United States. Conceptualization, H.C. J.D. S.L. P.D.S. K.-K.W. T.M. and J.D.W.; Validation, H.C. J.D. S.L. L.D. and H.Z.; Formal Analysis, H.C. J.D. S.L. S.H. and D.R.; Investigation, H.C. J.D. S.L. T.S. E.J.B. and J.B.; Writing – Original Draft, H.C. J.D. and S.L.; Writing – Review & Editing, H.C. J.D. S.L. T.S. E.A.A. T.M. and J.D.W.; Visualization, H.C. J.D. and S.L.; Supervision, T.M. J.D.W. and K.-K.W. P.D.S. is an employee and shareholder of AstraZeneca. T.M. is a cofounder and holds an equity in IMVAQ Therapeutics. He is a consultant of Immunos Therapeutics and Pfizer. He has research support from Bristol-Myers Squibb; Surface Oncology; Kyn Therapeutics; Infinity Pharmaceuticals, Inc.; Peregrine Pharmeceuticals, Inc.; Adaptive Biotechnologies; Leap Therapeutics, Inc.; and Aprea. He has patents on applications related to work on oncolytic viral therapy, alpha virus-based vaccine, neo antigen modeling, CD40, GITR, OX40, PD-1, and CTLA-4. K.K.W. is a founder and equity holder of G1 Therapeutics. He has sponsored research agreements with MedImmune, Takeda, TargImmune, and BMS. He also has consulting and sponsored research agreements with AstraZeneca, Janssen, Pfizer, Novartis, Merck, Ono, and Array. J.D.W. is a consultant for Adaptive Biotech; Advaxis; Amgen; Apricity; Array BioPharma; Ascentage Pharma; Astellas; Bayer; Beigene; Bristol Myers Squibb; Celgene; Chugai; Elucida; Eli Lilly; F Star; Genentech; Imvaq; Janssen; Kleo Pharma; Linneaus; MedImmune; Merck; Neon Therapuetics; Ono; Polaris Pharma; Polynoma; Psioxus; Puretech; Recepta; Trieza; Sellas Life Sciences; Serametrix; Surface Oncology; and Syndax. He has research support from Bristol Myers Squibb, Medimmune, and Genentech. He holds equity in Potenza Therapeutics; Tizona Pharmaceuticals; Adaptive Biotechnologies; Elucida; Imvaq; Beigene; Trieza; and Linneaus and has an honorarium from Esanex. He has patents of xenogeneic DNA vaccines (royalties); alphavirus replicon particles expressing TRP2; myeloid-derived suppressor cell (MDSC) assay (royalties); Newcastle disease viruses for cancer therapy; a genomic signature to identify responders to ipilimumab in melanoma; engineered vaccinia viruses for cancer immunotherapy; an anti-CD40 agonist monoclonal antibody (mAb) fused to monophosphoryl lipid A (MPL) for cancer therapy; CAR T cells targeting differentiation antigens as means to treat cancer; an anti-PD1 antibody; anti-CTLA4 antibodies; and anti-GITR antibodies and methods of use thereof. The other authors declare no competing interests. Funding Information: We thank Nouraiz Falik for the work on validation animal experiments. This research was funded in part through a Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant (SU2C-AACR-DT17-15); NIH-NCI Cancer Center Support grant P30 CA008748; the Ludwig Collaborative and Swim Across America Laboratory; Memorial Sloan Kettering Cancer Center, United States; the Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center; the Department of Medicine, Memorial Sloan Kettering Cancer Center; and Weill Cornell Medicine, United States. Conceptualization, H.C. J.D. S.L. P.D.S. K.-K.W. T.M. and J.D.W.; Validation, H.C. J.D. S.L. L.D. and H.Z.; Formal Analysis, H.C. J.D. S.L. S.H. and D.R.; Investigation, H.C. J.D. S.L. T.S. E.J.B. and J.B.; Writing ? Original Draft, H.C. J.D. and S.L.; Writing ? Review & Editing, H.C. J.D. S.L. T.S. E.A.A. T.M. and J.D.W.; Visualization, H.C. J.D. and S.L.; Supervision, T.M. J.D.W. and K.-K.W. P.D.S. is an employee and shareholder of AstraZeneca. T.M. is a cofounder and holds an equity in IMVAQ Therapeutics. He is a consultant of Immunos Therapeutics and Pfizer. He has research support from Bristol-Myers Squibb; Surface Oncology; Kyn Therapeutics; Infinity Pharmaceuticals, Inc.; Peregrine Pharmeceuticals, Inc.; Adaptive Biotechnologies; Leap Therapeutics, Inc.; and Aprea. He has patents on applications related to work on oncolytic viral therapy, alpha virus-based vaccine, neo antigen modeling, CD40, GITR, OX40, PD-1, and CTLA-4. K.K.W. is a founder and equity holder of G1 Therapeutics. He has sponsored research agreements with MedImmune, Takeda, TargImmune, and BMS. He also has consulting and sponsored research agreements with AstraZeneca, Janssen, Pfizer, Novartis, Merck, Ono, and Array. J.D.W. is a consultant for Adaptive Biotech; Advaxis; Amgen; Apricity; Array BioPharma; Ascentage Pharma; Astellas; Bayer; Beigene; Bristol Myers Squibb; Celgene; Chugai; Elucida; Eli Lilly; F Star; Genentech; Imvaq; Janssen; Kleo Pharma; Linneaus; MedImmune; Merck; Neon Therapuetics; Ono; Polaris Pharma; Polynoma; Psioxus; Puretech; Recepta; Trieza; Sellas Life Sciences; Serametrix; Surface Oncology; and Syndax. He has research support from Bristol Myers Squibb, Medimmune, and Genentech. He holds equity in Potenza Therapeutics; Tizona Pharmaceuticals; Adaptive Biotechnologies; Elucida; Imvaq; Beigene; Trieza; and Linneaus and has an honorarium from Esanex. He has patents of xenogeneic DNA vaccines (royalties); alphavirus replicon particles expressing TRP2; myeloid-derived suppressor cell (MDSC) assay (royalties); Newcastle disease viruses for cancer therapy; a genomic signature to identify responders to ipilimumab in melanoma; engineered vaccinia viruses for cancer immunotherapy; an anti-CD40 agonist monoclonal antibody (mAb) fused to monophosphoryl lipid A (MPL) for cancer therapy; CAR T cells targeting differentiation antigens as means to treat cancer; an anti-PD1 antibody; anti-CTLA4 antibodies; and anti-GITR antibodies and methods of use thereof. The other authors declare no competing interests. Publisher Copyright: © 2019 The Authors
PY - 2019/4/16
Y1 - 2019/4/16
N2 - KRAS mutant non-small-cell lung cancer (NSCLC) remains refractory to targeted therapeutics. Choi et al. show that pulsatile, rather than continuous, treatment with MEK inhibitors can maintain T cell activity better and prolong survival in mice with Kras mutant cancer. This effect is further enhanced when combined with CTLA-4 blockade.
AB - KRAS mutant non-small-cell lung cancer (NSCLC) remains refractory to targeted therapeutics. Choi et al. show that pulsatile, rather than continuous, treatment with MEK inhibitors can maintain T cell activity better and prolong survival in mice with Kras mutant cancer. This effect is further enhanced when combined with CTLA-4 blockade.
UR - http://www.scopus.com/inward/record.url?scp=85064175042&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85064175042&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2019.03.066
DO - 10.1016/j.celrep.2019.03.066
M3 - Article
C2 - 30995478
AN - SCOPUS:85064175042
SN - 2211-1247
VL - 27
SP - 806-819.e5
JO - Cell Reports
JF - Cell Reports
IS - 3
ER -