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Immunogenic chemotherapy enhances recruitment of CAR-T cells to lung tumors and improves antitumor efficacy when combined with checkpoint blockade

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Immunogenic chemotherapy enhances recruitment of CAR-T cells to lung tumors and improves antitumor efficacy when combined with checkpoint blockade. / Srivastava, Shivani; Furlan, Scott N; Jaeger-Ruckstuhl, Carla; Sarvothama, Megha; Berger, Susanna Carolina; Smythe, Kimberly S; Garrison, Sarah M; Specht, Jennifer M; Lee, Sylvia M; Amezquita, Robert A; Viollet, Valentin; Muhunthan, Vishaka ; Yechan-Gunja, Sushma; Pillai, Smitha PS; Rader, Christoph; Houghton, A McGarry; Pierce, Robert H; Gottardo, Raphael; Maloney, David G; Riddell, Stanley R.

In: CANCER CELL, Vol. 39, No. 2, 08.02.2021, p. 193-208.e10.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Srivastava, S, Furlan, SN, Jaeger-Ruckstuhl, C, Sarvothama, M, Berger, SC, Smythe, KS, Garrison, SM, Specht, JM, Lee, SM, Amezquita, RA, Viollet, V, Muhunthan, V, Yechan-Gunja, S, Pillai, SPS, Rader, C, Houghton, AM, Pierce, RH, Gottardo, R, Maloney, DG & Riddell, SR 2021, 'Immunogenic chemotherapy enhances recruitment of CAR-T cells to lung tumors and improves antitumor efficacy when combined with checkpoint blockade', CANCER CELL, vol. 39, no. 2, pp. 193-208.e10. https://doi.org/10.1016/j.ccell.2020.11.005

APA

Srivastava, S., Furlan, S. N., Jaeger-Ruckstuhl, C., Sarvothama, M., Berger, S. C., Smythe, K. S., Garrison, S. M., Specht, J. M., Lee, S. M., Amezquita, R. A., Viollet, V., Muhunthan, V., Yechan-Gunja, S., Pillai, S. PS., Rader, C., Houghton, A. M., Pierce, R. H., Gottardo, R., Maloney, D. G., & Riddell, S. R. (2021). Immunogenic chemotherapy enhances recruitment of CAR-T cells to lung tumors and improves antitumor efficacy when combined with checkpoint blockade. CANCER CELL, 39(2), 193-208.e10. https://doi.org/10.1016/j.ccell.2020.11.005

Vancouver

Srivastava S, Furlan SN, Jaeger-Ruckstuhl C, Sarvothama M, Berger SC, Smythe KS et al. Immunogenic chemotherapy enhances recruitment of CAR-T cells to lung tumors and improves antitumor efficacy when combined with checkpoint blockade. CANCER CELL. 2021 Feb 8;39(2):193-208.e10. https://doi.org/10.1016/j.ccell.2020.11.005

Bibtex

@article{67852c5bc9b84cda9c4f8c7328b8e203,
title = "Immunogenic chemotherapy enhances recruitment of CAR-T cells to lung tumors and improves antitumor efficacy when combined with checkpoint blockade",
abstract = "Adoptive therapy using chimeric antigen receptor-modified T cells (CAR-T cells) is effective in hematologic but not epithelial malignancies, which cause the greatest mortality. In breast and lung cancer patients, CAR-T cells targeting the tumor-associated antigen receptor tyrosine kinase-like orphan receptor 1 (ROR1) infiltrate tumors poorly and become dysfunctional. To test strategies for enhancing efficacy, we adapted the KrasLSL-G12D/+;p53f/f autochthonous model of lung adenocarcinoma to express the CAR target ROR1. Murine ROR1 CAR-T cells transferred after lymphodepletion with cyclophosphamide (Cy) transiently control tumor growth but infiltrate tumors poorly and lose function, similar to what is seen in patients. Adding oxaliplatin (Ox) to the lymphodepletion regimen activates tumor macrophages to express T-cell-recruiting chemokines, resulting in improved CAR-T cell infiltration, remodeling of the tumor microenvironment, and increased tumor sensitivity to anti-PD-L1. Combination therapy with Ox/Cy and anti-PD-L1 synergistically improves CAR-T cell-mediated tumor control and survival, providing a strategy to improve CAR-T cell efficacy in the clinic.",
author = "Shivani Srivastava and Furlan, {Scott N} and Carla Jaeger-Ruckstuhl and Megha Sarvothama and Berger, {Susanna Carolina} and Smythe, {Kimberly S} and Garrison, {Sarah M} and Specht, {Jennifer M} and Lee, {Sylvia M} and Amezquita, {Robert A} and Valentin Viollet and Vishaka Muhunthan and Sushma Yechan-Gunja and Pillai, {Smitha PS} and Christoph Rader and Houghton, {A McGarry} and Pierce, {Robert H} and Raphael Gottardo and Maloney, {David G} and Riddell, {Stanley R}",
year = "2021",
month = feb,
day = "8",
doi = "10.1016/j.ccell.2020.11.005",
language = "English",
volume = "39",
pages = "193--208.e10",
journal = "CANCER CELL",
issn = "1535-6108",
publisher = "Cell Press",
number = "2",

}

RIS

TY - JOUR

T1 - Immunogenic chemotherapy enhances recruitment of CAR-T cells to lung tumors and improves antitumor efficacy when combined with checkpoint blockade

AU - Srivastava, Shivani

AU - Furlan, Scott N

AU - Jaeger-Ruckstuhl, Carla

AU - Sarvothama, Megha

AU - Berger, Susanna Carolina

AU - Smythe, Kimberly S

AU - Garrison, Sarah M

AU - Specht, Jennifer M

AU - Lee, Sylvia M

AU - Amezquita, Robert A

AU - Viollet, Valentin

AU - Muhunthan, Vishaka

AU - Yechan-Gunja, Sushma

AU - Pillai, Smitha PS

AU - Rader, Christoph

AU - Houghton, A McGarry

AU - Pierce, Robert H

AU - Gottardo, Raphael

AU - Maloney, David G

AU - Riddell, Stanley R

PY - 2021/2/8

Y1 - 2021/2/8

N2 - Adoptive therapy using chimeric antigen receptor-modified T cells (CAR-T cells) is effective in hematologic but not epithelial malignancies, which cause the greatest mortality. In breast and lung cancer patients, CAR-T cells targeting the tumor-associated antigen receptor tyrosine kinase-like orphan receptor 1 (ROR1) infiltrate tumors poorly and become dysfunctional. To test strategies for enhancing efficacy, we adapted the KrasLSL-G12D/+;p53f/f autochthonous model of lung adenocarcinoma to express the CAR target ROR1. Murine ROR1 CAR-T cells transferred after lymphodepletion with cyclophosphamide (Cy) transiently control tumor growth but infiltrate tumors poorly and lose function, similar to what is seen in patients. Adding oxaliplatin (Ox) to the lymphodepletion regimen activates tumor macrophages to express T-cell-recruiting chemokines, resulting in improved CAR-T cell infiltration, remodeling of the tumor microenvironment, and increased tumor sensitivity to anti-PD-L1. Combination therapy with Ox/Cy and anti-PD-L1 synergistically improves CAR-T cell-mediated tumor control and survival, providing a strategy to improve CAR-T cell efficacy in the clinic.

AB - Adoptive therapy using chimeric antigen receptor-modified T cells (CAR-T cells) is effective in hematologic but not epithelial malignancies, which cause the greatest mortality. In breast and lung cancer patients, CAR-T cells targeting the tumor-associated antigen receptor tyrosine kinase-like orphan receptor 1 (ROR1) infiltrate tumors poorly and become dysfunctional. To test strategies for enhancing efficacy, we adapted the KrasLSL-G12D/+;p53f/f autochthonous model of lung adenocarcinoma to express the CAR target ROR1. Murine ROR1 CAR-T cells transferred after lymphodepletion with cyclophosphamide (Cy) transiently control tumor growth but infiltrate tumors poorly and lose function, similar to what is seen in patients. Adding oxaliplatin (Ox) to the lymphodepletion regimen activates tumor macrophages to express T-cell-recruiting chemokines, resulting in improved CAR-T cell infiltration, remodeling of the tumor microenvironment, and increased tumor sensitivity to anti-PD-L1. Combination therapy with Ox/Cy and anti-PD-L1 synergistically improves CAR-T cell-mediated tumor control and survival, providing a strategy to improve CAR-T cell efficacy in the clinic.

U2 - 10.1016/j.ccell.2020.11.005

DO - 10.1016/j.ccell.2020.11.005

M3 - SCORING: Journal article

VL - 39

SP - 193-208.e10

JO - CANCER CELL

JF - CANCER CELL

SN - 1535-6108

IS - 2

ER -